ES2481042T3 - Derivados de 2-piridin-2-il-pirazol-3(2H)-ona, su preparación y uso terapéutico como activadores de HIF - Google Patents

Derivados de 2-piridin-2-il-pirazol-3(2H)-ona, su preparación y uso terapéutico como activadores de HIF Download PDF

Info

Publication number: ES2481042T3
Authority: ES; Spain
Prior art keywords: pyrazol; dihydro; methyl; oxo; group
Prior art date: 2008-12-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES09805789.6T

Other languages

English (en)

Spanish (es)

Inventor

Jean-Michel Altenburger

Valérie FOSSEY

Stéphane ILLIANO

Géraldine MANETTE

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi SA

Original Assignee

Sanofi SA

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2008-12-29

Filing date

2009-12-24

Publication date

2014-07-29

2008-12-29 Priority claimed from FR0807474A external-priority patent/FR2940651B1/fr

2009-08-28 Priority claimed from FR0904092A external-priority patent/FR2949466A1/fr

2009-12-24 Application filed by Sanofi SA filed Critical Sanofi SA

2014-07-29 Application granted granted Critical

2014-07-29 Publication of ES2481042T3 publication Critical patent/ES2481042T3/es

Status Active legal-status Critical Current

2029-12-24 Anticipated expiration legal-status Critical

Links

238000002360 preparation method Methods 0.000 title claims description 15
239000012190 activator Substances 0.000 title description 6
230000001225 therapeutic effect Effects 0.000 title description 4
UHZJGBKNLJRCMK-UHFFFAOYSA-N 2-pyridin-2-yl-1h-pyrazol-3-one Chemical class O=C1C=CNN1C1=CC=CC=N1 UHZJGBKNLJRCMK-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 220
125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 59
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract description 52
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 38
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
125000003118 aryl group Chemical group 0.000 claims abstract description 28
229910052799 carbon Inorganic materials 0.000 claims abstract description 24
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 23
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 22
125000001424 substituent group Chemical group 0.000 claims abstract description 22
125000006833 (C1-C5) alkylene group Chemical group 0.000 claims abstract description 21
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
125000005843 halogen group Chemical group 0.000 claims abstract description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 13
101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims abstract description 10
125000002993 cycloalkylene group Chemical group 0.000 claims abstract description 9
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
-1 hexamethyleneimino group Chemical group 0.000 claims description 146
238000000034 method Methods 0.000 claims description 100
125000000217 alkyl group Chemical group 0.000 claims description 81
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 30
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 28
238000011282 treatment Methods 0.000 claims description 23
239000003814 drug Substances 0.000 claims description 20
229940124530 sulfonamide Drugs 0.000 claims description 19
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
125000005842 heteroatom Chemical group 0.000 claims description 14
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 10
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 8
208000007502 anemia Diseases 0.000 claims description 8
229940079593 drug Drugs 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 7
238000011321 prophylaxis Methods 0.000 claims description 7
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 6
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
230000000302 ischemic effect Effects 0.000 claims description 6
NUQWAHHXKTUPPG-UHFFFAOYSA-N n,n-dimethyl-6-[5-methyl-3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]pyridine-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)N(C)C)=CC=C1N1C(=O)C(CC=2C=NC=CC=2)=C(C)N1 NUQWAHHXKTUPPG-UHFFFAOYSA-N 0.000 claims description 6
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
ACOWDFGPPZPERV-UHFFFAOYSA-N 2-[2-[5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]acetic acid Chemical compound C=1C=C(N2C(C(CC(O)=O)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ACOWDFGPPZPERV-UHFFFAOYSA-N 0.000 claims description 5
RAHTXPUIMOXOBO-UHFFFAOYSA-N 2-[5-(benzenesulfonyl)pyridin-2-yl]-5-methyl-4-(pyridin-3-ylmethyl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=NC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)C1=CC=CC=C1 RAHTXPUIMOXOBO-UHFFFAOYSA-N 0.000 claims description 5
125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
JZGCCTVQYAJAPU-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-(2,3-dihydroxypropyl)-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CC(O)CO)C1=CC=CC=C1 JZGCCTVQYAJAPU-UHFFFAOYSA-N 0.000 claims description 5
KSRPTDBDBDBTRM-PKOBYXMFSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-[(1r,3s)-3-(hydroxymethyl)cyclopentyl]-n-methylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(C)[C@@H]1CC[C@H](CO)C1 KSRPTDBDBDBTRM-PKOBYXMFSA-N 0.000 claims description 5
PNZLSOKNLIGAFG-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-cyclopentyl-n-(3-hydroxypropyl)pyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CCCO)C1CCCC1 PNZLSOKNLIGAFG-UHFFFAOYSA-N 0.000 claims description 5
RKIYLLCTDXNVTR-UHFFFAOYSA-N 6-[4-[(5-cyanopyridin-3-yl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(C=NC=3)C#N)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 RKIYLLCTDXNVTR-UHFFFAOYSA-N 0.000 claims description 5
NWTWLJYVDJMCJY-UHFFFAOYSA-N 6-[4-[[3-(dimethylamino)phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(C=CC=3)N(C)C)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 NWTWLJYVDJMCJY-UHFFFAOYSA-N 0.000 claims description 5
208000010412 Glaucoma Diseases 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
208000028867 ischemia Diseases 0.000 claims description 5
QRMCQWZZKGGKTG-UHFFFAOYSA-N n-ethyl-6-[4-[(4-methoxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(OC)=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 QRMCQWZZKGGKTG-UHFFFAOYSA-N 0.000 claims description 5
VVVWCTRBAUECEL-UHFFFAOYSA-N n-ethyl-6-[4-[[3-(2-methoxyethoxy)phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(OCCOC)C=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 VVVWCTRBAUECEL-UHFFFAOYSA-N 0.000 claims description 5
JMVYCOFETVCOQQ-UHFFFAOYSA-N n-ethyl-6-[4-[[3-(methoxymethyl)phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(COC)C=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 JMVYCOFETVCOQQ-UHFFFAOYSA-N 0.000 claims description 5
ZDTFJXLNIBOGPW-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(1-phenylcyclopropyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(=C(C)N2)C2(CC2)C=2C=CC=CC=2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZDTFJXLNIBOGPW-UHFFFAOYSA-N 0.000 claims description 5
RYNLGKVNIIXAAS-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(2-phenylethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CCC=3C=CC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 RYNLGKVNIIXAAS-UHFFFAOYSA-N 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
NKFLEFWUYAUDJV-UHFFFAOYSA-N pyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1 NKFLEFWUYAUDJV-UHFFFAOYSA-N 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
FADOXZTXZKJINV-UHFFFAOYSA-N 2-[2-[5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]-n-methylacetamide Chemical compound C=1C=C(N2C(C(CC(=O)NC)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 FADOXZTXZKJINV-UHFFFAOYSA-N 0.000 claims description 4
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
STDSOUDGVBIHGX-UHFFFAOYSA-N 3-[2-[5-[cyclopentyl(methyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]-3-phenyl-n-(2,2,2-trifluoroethyl)propanamide Chemical compound C=1C=C(N2C(C(C(CC(=O)NCC(F)(F)F)C=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(C)C1CCCC1 STDSOUDGVBIHGX-UHFFFAOYSA-N 0.000 claims description 4
SGGHYUWVEHYKKU-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-cyclopentyl-n-(3-phenylmethoxypropyl)pyridine-3-sulfonamide Chemical compound C=1NN(C=2N=CC(=CC=2)S(=O)(=O)N(CCCOCC=2C=CC=CC=2)C2CCCC2)C(=O)C=1CC1=CC=CC=C1 SGGHYUWVEHYKKU-UHFFFAOYSA-N 0.000 claims description 4
ZSOMULJXIHQCEO-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZSOMULJXIHQCEO-UHFFFAOYSA-N 0.000 claims description 4
PWRICYWQXCROAT-UHFFFAOYSA-N 6-[4-benzyl-3-oxo-5-(trifluoromethyl)-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=C(N2)C(F)(F)F)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 PWRICYWQXCROAT-UHFFFAOYSA-N 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
230000000747 cardiac effect Effects 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
GACGPHSDGVFQGM-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(2-phenylpropan-2-yl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(=C(C)N2)C(C)(C)C=2C=CC=CC=2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 GACGPHSDGVFQGM-UHFFFAOYSA-N 0.000 claims description 4
RQDJNWKBJFAXSJ-UHFFFAOYSA-N n-tert-butyl-6-[3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]pyridine-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)NC(C)(C)C)=CC=C1N1C(=O)C(CC=2C=NC=CC=2)=CN1 RQDJNWKBJFAXSJ-UHFFFAOYSA-N 0.000 claims description 4
RXDJVRLGXYUBNS-UHFFFAOYSA-N n-tert-butyl-6-[3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]pyridine-3-sulfonamide;hydrochloride Chemical compound Cl.N1=CC(S(=O)(=O)NC(C)(C)C)=CC=C1N1C(=O)C(CC=2C=NC=CC=2)=CN1 RXDJVRLGXYUBNS-UHFFFAOYSA-N 0.000 claims description 4
229910052721 tungsten Inorganic materials 0.000 claims description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims description 3
206010002383 Angina Pectoris Diseases 0.000 claims description 3
206010003210 Arteriosclerosis Diseases 0.000 claims description 3
208000014644 Brain disease Diseases 0.000 claims description 3
208000024172 Cardiovascular disease Diseases 0.000 claims description 3
208000034657 Convalescence Diseases 0.000 claims description 3
QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 3
208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
239000008280 blood Substances 0.000 claims description 3
210000004369 blood Anatomy 0.000 claims description 3
206010012601 diabetes mellitus Diseases 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
230000035876 healing Effects 0.000 claims description 3
208000017169 kidney disease Diseases 0.000 claims description 3
229940095102 methyl benzoate Drugs 0.000 claims description 3
CXFZTRUCHRVGSG-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=NC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 CXFZTRUCHRVGSG-UHFFFAOYSA-N 0.000 claims description 3
230000000626 neurodegenerative effect Effects 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
230000002980 postoperative effect Effects 0.000 claims description 3
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
238000011477 surgical intervention Methods 0.000 claims description 3
238000001356 surgical procedure Methods 0.000 claims description 3
210000000115 thoracic cavity Anatomy 0.000 claims description 3
230000002792 vascular Effects 0.000 claims description 3
XDRYETFTRPTRDK-UHFFFAOYSA-N 2-[(5-methyl-3-oxo-2-pyridin-2-yl-1h-pyrazol-4-yl)methyl]benzonitrile Chemical compound O=C1C(CC=2C(=CC=CC=2)C#N)=C(C)NN1C1=CC=CC=N1 XDRYETFTRPTRDK-UHFFFAOYSA-N 0.000 claims description 2
SKQVPJOGELCRDJ-UHFFFAOYSA-N 2-[2-[5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]-n,n-dimethylacetamide Chemical compound C=1C=C(N2C(C(CC(=O)N(C)C)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 SKQVPJOGELCRDJ-UHFFFAOYSA-N 0.000 claims description 2
WNANDSHIFLXLKF-UHFFFAOYSA-N 2-[5-(azepan-1-ylsulfonyl)pyridin-2-yl]-4-(pyridin-3-ylmethyl)-1h-pyrazol-3-one Chemical compound C=1NN(C=2N=CC(=CC=2)S(=O)(=O)N2CCCCCC2)C(=O)C=1CC1=CC=CN=C1 WNANDSHIFLXLKF-UHFFFAOYSA-N 0.000 claims description 2
MZDIODQGOIUJFJ-UHFFFAOYSA-N 2-[5-(azepan-1-ylsulfonyl)pyridin-2-yl]-4-benzyl-5-methyl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCCC1 MZDIODQGOIUJFJ-UHFFFAOYSA-N 0.000 claims description 2
BFZZBMBRJGIZTL-UHFFFAOYSA-N 3-[(5-methyl-3-oxo-2-pyridin-2-yl-1h-pyrazol-4-yl)methyl]benzonitrile Chemical compound O=C1C(CC=2C=C(C=CC=2)C#N)=C(C)NN1C1=CC=CC=N1 BFZZBMBRJGIZTL-UHFFFAOYSA-N 0.000 claims description 2
ZHOAHJFQLDGAOE-UHFFFAOYSA-N 3-[2-[5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]propanoic acid Chemical compound C=1C=C(N2C(C(CCC(O)=O)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZHOAHJFQLDGAOE-UHFFFAOYSA-N 0.000 claims description 2
KOOYFMSQDIAYBJ-UHFFFAOYSA-N 4-(1,1-dioxothiolan-3-yl)-5-methyl-2-(5-piperidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(C2CS(=O)(=O)CC2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCC1 KOOYFMSQDIAYBJ-UHFFFAOYSA-N 0.000 claims description 2
JLUGCTVRRPVNAZ-GASCZTMLSA-N 4-[(2,4-dichlorophenyl)methyl]-2-[5-[(3s,5r)-3,5-dimethylpiperidin-1-yl]sulfonylpyridin-2-yl]-5-methyl-1h-pyrazol-3-one Chemical compound C1[C@@H](C)C[C@@H](C)CN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C(=CC(Cl)=CC=3)Cl)=C(C)N2)=O)N=C1 JLUGCTVRRPVNAZ-GASCZTMLSA-N 0.000 claims description 2
HQIMAUOJGJNXEX-UHFFFAOYSA-N 4-[(2,4-dichlorophenyl)methyl]-5-methyl-2-(5-piperidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC(Cl)=CC=2)Cl)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCC1 HQIMAUOJGJNXEX-UHFFFAOYSA-N 0.000 claims description 2
SOAVYYGIXBZADM-UHFFFAOYSA-N 4-[(2,4-dichlorophenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC(Cl)=CC=2)Cl)=C(C)NN1C1=CC=CC=N1 SOAVYYGIXBZADM-UHFFFAOYSA-N 0.000 claims description 2
PNFWQMYSXXNCPH-UHFFFAOYSA-N 4-[(2,5-dimethoxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound COC1=CC=C(OC)C(CC=2C(N(C=3N=CC=CC=3)NC=2C)=O)=C1 PNFWQMYSXXNCPH-UHFFFAOYSA-N 0.000 claims description 2
VGGRLXOEFPMJCS-UHFFFAOYSA-N 4-[(2-chloro-6-fluorophenyl)methyl]-5-methyl-2-(5-piperidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2F)Cl)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCC1 VGGRLXOEFPMJCS-UHFFFAOYSA-N 0.000 claims description 2
NHOHFMDYFQYGNF-UHFFFAOYSA-N 4-[(2-chloro-6-fluorophenyl)methyl]-5-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2F)Cl)=C(C)NN1C1=CC=C(C(F)(F)F)C=N1 NHOHFMDYFQYGNF-UHFFFAOYSA-N 0.000 claims description 2
ZHMHADSDFXLZDQ-IYBDPMFKSA-N 4-[(2-chlorophenyl)methyl]-2-[5-[(3r,5s)-3,5-dimethylpiperidin-1-yl]sulfonylpyridin-2-yl]-5-methyl-1h-pyrazol-3-one Chemical compound C1[C@@H](C)C[C@@H](C)CN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C(=CC=CC=3)Cl)=C(C)N2)=O)N=C1 ZHMHADSDFXLZDQ-IYBDPMFKSA-N 0.000 claims description 2
ALKGAYRQGFESOA-UHFFFAOYSA-N 4-[(2-chlorophenyl)methyl]-5-methyl-2-(5-piperidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)Cl)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCC1 ALKGAYRQGFESOA-UHFFFAOYSA-N 0.000 claims description 2
ADHFCQJXNUOSGV-UHFFFAOYSA-N 4-[(2-chlorophenyl)methyl]-5-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)Cl)=C(C)NN1C1=CC=C(C(F)(F)F)C=N1 ADHFCQJXNUOSGV-UHFFFAOYSA-N 0.000 claims description 2
CXMLXVBGVHYTOX-UHFFFAOYSA-N 4-[(2-chlorophenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)Cl)=C(C)NN1C1=CC=CC=N1 CXMLXVBGVHYTOX-UHFFFAOYSA-N 0.000 claims description 2
HTPHVRADCYFYJX-UHFFFAOYSA-N 4-[(2-fluorophenyl)methyl]-5-methyl-2-(5-piperidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)F)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCC1 HTPHVRADCYFYJX-UHFFFAOYSA-N 0.000 claims description 2
ZNIULWMYGWJPET-UHFFFAOYSA-N 4-[(2-fluorophenyl)methyl]-5-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)F)=C(C)NN1C1=CC=C(C(F)(F)F)C=N1 ZNIULWMYGWJPET-UHFFFAOYSA-N 0.000 claims description 2
LPTUYWJMTIGWLZ-UHFFFAOYSA-N 4-[(2-fluorophenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)F)=C(C)NN1C1=CC=CC=N1 LPTUYWJMTIGWLZ-UHFFFAOYSA-N 0.000 claims description 2
QLDGNQNOISNGLA-UHFFFAOYSA-N 4-[(2-methoxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound COC1=CC=CC=C1CC(C1=O)=C(C)NN1C1=CC=CC=N1 QLDGNQNOISNGLA-UHFFFAOYSA-N 0.000 claims description 2
WFUPHWTWFGCTHT-UHFFFAOYSA-N 4-[(3,5-dimethoxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound COC1=CC(OC)=CC(CC=2C(N(C=3N=CC=CC=3)NC=2C)=O)=C1 WFUPHWTWFGCTHT-UHFFFAOYSA-N 0.000 claims description 2
ZDXMDOPQCONNOO-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=C(O)C=CC=2)=C(C)NN1C1=CC=CC=N1 ZDXMDOPQCONNOO-UHFFFAOYSA-N 0.000 claims description 2
SRFOVRCOAMIVIB-UHFFFAOYSA-N 4-[(3-methoxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound COC1=CC=CC(CC=2C(N(C=3N=CC=CC=3)NC=2C)=O)=C1 SRFOVRCOAMIVIB-UHFFFAOYSA-N 0.000 claims description 2
ZFVZYNYJCHCNQZ-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-5-methyl-2-(5-piperidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC(Cl)=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCCC1 ZFVZYNYJCHCNQZ-UHFFFAOYSA-N 0.000 claims description 2
VKUPYIZWDYNUGU-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC(Cl)=CC=2)=C(C)NN1C1=CC=CC=N1 VKUPYIZWDYNUGU-UHFFFAOYSA-N 0.000 claims description 2
ZVGVMASQNLDHLN-UHFFFAOYSA-N 4-[(4-hydroxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC(O)=CC=2)=C(C)NN1C1=CC=CC=N1 ZVGVMASQNLDHLN-UHFFFAOYSA-N 0.000 claims description 2
FXTVLQUZNSXMDB-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound C1=CC(OC)=CC=C1CC(C1=O)=C(C)NN1C1=CC=CC=N1 FXTVLQUZNSXMDB-UHFFFAOYSA-N 0.000 claims description 2
GOCGAQMYIKKAQL-UHFFFAOYSA-N 4-[(5-methyl-3-oxo-2-pyridin-2-yl-1h-pyrazol-4-yl)methyl]benzonitrile Chemical compound O=C1C(CC=2C=CC(=CC=2)C#N)=C(C)NN1C1=CC=CC=N1 GOCGAQMYIKKAQL-UHFFFAOYSA-N 0.000 claims description 2
VEBKKSHXOKRMCJ-UHFFFAOYSA-N 4-[[3-(dimethylamino)phenyl]methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound CN(C)C1=CC=CC(CC=2C(N(C=3N=CC=CC=3)NC=2C)=O)=C1 VEBKKSHXOKRMCJ-UHFFFAOYSA-N 0.000 claims description 2
DSLXLAGDYGWPQG-UHFFFAOYSA-N 4-[[3-(methoxymethyl)phenyl]methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound COCC1=CC=CC(CC=2C(N(C=3N=CC=CC=3)NC=2C)=O)=C1 DSLXLAGDYGWPQG-UHFFFAOYSA-N 0.000 claims description 2
SVAKKHCTYASURM-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound C1=CC(N(C)C)=CC=C1CC(C1=O)=C(C)NN1C1=CC=CC=N1 SVAKKHCTYASURM-UHFFFAOYSA-N 0.000 claims description 2
PPWUFTBLURXYGF-UHFFFAOYSA-N 4-benzyl-2-(5-bromopyridin-2-yl)-5-methyl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC=CC=2)=C(C)NN1C1=CC=C(Br)C=N1 PPWUFTBLURXYGF-UHFFFAOYSA-N 0.000 claims description 2
SOSMCUDETTZDET-GOSISDBHSA-N 4-benzyl-2-[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]sulfonylpyridin-2-yl]-1h-pyrazol-3-one Chemical compound C1[C@H](N(C)C)CCN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=C1 SOSMCUDETTZDET-GOSISDBHSA-N 0.000 claims description 2
OCINMTAXDUIZGO-UHFFFAOYSA-N 4-benzyl-2-[5-[(4-methyl-1,4-diazepan-1-yl)sulfonyl]pyridin-2-yl]-1h-pyrazol-3-one Chemical compound C1CN(C)CCCN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=C1 OCINMTAXDUIZGO-UHFFFAOYSA-N 0.000 claims description 2
PAZQANGQMUKBTD-UHFFFAOYSA-N 4-benzyl-5-ethyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC=CC=2)=C(CC)NN1C1=CC=CC=N1 PAZQANGQMUKBTD-UHFFFAOYSA-N 0.000 claims description 2
ZKHAZBYINAAOSX-UHFFFAOYSA-N 4-benzyl-5-methyl-2-(5-morpholin-4-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCOCC1 ZKHAZBYINAAOSX-UHFFFAOYSA-N 0.000 claims description 2
WZWVQFKGRGOGBT-UHFFFAOYSA-N 4-benzyl-5-methyl-2-(5-pyrrolidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCC1 WZWVQFKGRGOGBT-UHFFFAOYSA-N 0.000 claims description 2
BNACOCOEQLPNMG-UHFFFAOYSA-N 4-benzyl-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC=CC=2)=C(C)NN1C1=CC=CC=N1 BNACOCOEQLPNMG-UHFFFAOYSA-N 0.000 claims description 2
RVKVPQDODAVVLP-UHFFFAOYSA-N 5-methyl-2-pyridin-2-yl-4-(pyridin-3-ylmethyl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=NC=CC=2)=C(C)NN1C1=CC=CC=N1 RVKVPQDODAVVLP-UHFFFAOYSA-N 0.000 claims description 2
ZCJBCYQENQNUIZ-UHFFFAOYSA-N 5-methyl-2-pyridin-2-yl-4-(pyridin-4-ylmethyl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CN=CC=2)=C(C)NN1C1=CC=CC=N1 ZCJBCYQENQNUIZ-UHFFFAOYSA-N 0.000 claims description 2
SKWKGGHPIUOCMD-UHFFFAOYSA-N 5-methyl-2-pyridin-2-yl-4-[[2-(trifluoromethyl)phenyl]methyl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC=CC=2)C(F)(F)F)=C(C)NN1C1=CC=CC=N1 SKWKGGHPIUOCMD-UHFFFAOYSA-N 0.000 claims description 2
ADDGNELFLROZGQ-UHFFFAOYSA-N 5-methyl-2-pyridin-2-yl-4-[[3-(trifluoromethyl)phenyl]methyl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=C(C=CC=2)C(F)(F)F)=C(C)NN1C1=CC=CC=N1 ADDGNELFLROZGQ-UHFFFAOYSA-N 0.000 claims description 2
ODBXFBQVYJDHPZ-UHFFFAOYSA-N 5-methyl-2-pyridin-2-yl-4-[[4-(trifluoromethyl)phenyl]methyl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC(=CC=2)C(F)(F)F)=C(C)NN1C1=CC=CC=N1 ODBXFBQVYJDHPZ-UHFFFAOYSA-N 0.000 claims description 2
WQFZZLNUKXMXRQ-UHFFFAOYSA-N 5-methyl-4-(2-phenylethyl)-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CCC=2C=CC=CC=2)=C(C)NN1C1=CC=CC=N1 WQFZZLNUKXMXRQ-UHFFFAOYSA-N 0.000 claims description 2
GZCPLEWLMSNCNR-UHFFFAOYSA-N 5-methyl-4-(pyridin-3-ylmethyl)-2-(5-pyrrolidin-1-ylsulfonylpyridin-2-yl)-1h-pyrazol-3-one;hydrochloride Chemical compound Cl.O=C1C(CC=2C=NC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N1CCCC1 GZCPLEWLMSNCNR-UHFFFAOYSA-N 0.000 claims description 2
WQGKVVFXYOJPKA-UHFFFAOYSA-N 5-methyl-4-[(4-methylsulfonylphenyl)methyl]-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=CC(=CC=2)S(C)(=O)=O)=C(C)NN1C1=CC=CC=N1 WQGKVVFXYOJPKA-UHFFFAOYSA-N 0.000 claims description 2
TWZJFCAGQGYXGK-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-cyclopentyl-n-(2-phenylmethoxyethyl)pyridine-3-sulfonamide Chemical compound C=1NN(C=2N=CC(=CC=2)S(=O)(=O)N(CCOCC=2C=CC=CC=2)C2CCCC2)C(=O)C=1CC1=CC=CC=C1 TWZJFCAGQGYXGK-UHFFFAOYSA-N 0.000 claims description 2
MYULSYBCMZBZCS-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-methyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(C)C1=CC=CC=C1 MYULSYBCMZBZCS-UHFFFAOYSA-N 0.000 claims description 2
SVMDUIQPJLTQST-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-tert-butyl-n-methylpyridine-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)N(C(C)(C)C)C)=CC=C1N1C(=O)C(CC=2C=CC=CC=2)=CN1 SVMDUIQPJLTQST-UHFFFAOYSA-N 0.000 claims description 2
QKDAPUFDOWGHLQ-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-5-propyl-1h-pyrazol-2-yl)-n-ethyl-n-phenylpyridine-3-sulfonamide;hydrochloride Chemical compound Cl.O=C1C(CC=2C=CC=CC=2)=C(CCC)NN1C(N=C1)=CC=C1S(=O)(=O)N(CC)C1=CC=CC=C1 QKDAPUFDOWGHLQ-UHFFFAOYSA-N 0.000 claims description 2
QQDIEGKWOMUGCK-UHFFFAOYSA-N 6-(4-benzyl-5-ethyl-3-oxo-1h-pyrazol-2-yl)-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=C(CC)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 QQDIEGKWOMUGCK-UHFFFAOYSA-N 0.000 claims description 2
SDFGRSXHEMOMML-UHFFFAOYSA-N 6-(4-benzyl-5-methyl-3-oxo-1h-pyrazol-2-yl)-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 SDFGRSXHEMOMML-UHFFFAOYSA-N 0.000 claims description 2
RPYPKZJZJDCMSY-UHFFFAOYSA-N 6-[4-(1,1-dioxothiolan-3-yl)-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(C3CS(=O)(=O)CC3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 RPYPKZJZJDCMSY-UHFFFAOYSA-N 0.000 claims description 2
SIVZEERHHXMHMA-UHFFFAOYSA-N 6-[4-(cyclopentylmethyl)-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC3CCCC3)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 SIVZEERHHXMHMA-UHFFFAOYSA-N 0.000 claims description 2
VQAZSWOHVPOTJE-UHFFFAOYSA-N 6-[4-[(2,4-dichlorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC(Cl)=CC=3)Cl)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 VQAZSWOHVPOTJE-UHFFFAOYSA-N 0.000 claims description 2
PYFLOYCESZIIMB-UHFFFAOYSA-N 6-[4-[(2,5-dimethoxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=C(OC)C=3)OC)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 PYFLOYCESZIIMB-UHFFFAOYSA-N 0.000 claims description 2
UMVNCKVGWLEGGL-UHFFFAOYSA-N 6-[4-[(2-chloro-6-fluorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n,n-diethylpyridine-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)N(CC)CC)=CC=C1N1C(=O)C(CC=2C(=CC=CC=2F)Cl)=C(C)N1 UMVNCKVGWLEGGL-UHFFFAOYSA-N 0.000 claims description 2
LGDXKNONLNVFIM-UHFFFAOYSA-N 6-[4-[(2-chloro-6-fluorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=CC=3F)Cl)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 LGDXKNONLNVFIM-UHFFFAOYSA-N 0.000 claims description 2
OJQCJIXIBIELFA-UHFFFAOYSA-N 6-[4-[(2-chlorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n,n-diethylpyridine-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)N(CC)CC)=CC=C1N1C(=O)C(CC=2C(=CC=CC=2)Cl)=C(C)N1 OJQCJIXIBIELFA-UHFFFAOYSA-N 0.000 claims description 2
ZBZWNVSJWYWIII-UHFFFAOYSA-N 6-[4-[(2-chlorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=CC=3)Cl)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZBZWNVSJWYWIII-UHFFFAOYSA-N 0.000 claims description 2
OQUYDSBQUCHFOL-UHFFFAOYSA-N 6-[4-[(2-chlorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]pyridine-3-carboxylic acid Chemical compound O=C1C(CC=2C(=CC=CC=2)Cl)=C(C)NN1C1=CC=C(C(O)=O)C=N1 OQUYDSBQUCHFOL-UHFFFAOYSA-N 0.000 claims description 2
OYQUFTDKYZSDIB-UHFFFAOYSA-N 6-[4-[(2-cyanophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=CC=3)C#N)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 OYQUFTDKYZSDIB-UHFFFAOYSA-N 0.000 claims description 2
RCJGDDKJGKOOTG-UHFFFAOYSA-N 6-[4-[(3-cyanophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(C=CC=3)C#N)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 RCJGDDKJGKOOTG-UHFFFAOYSA-N 0.000 claims description 2
LGSSUTQKTCIAEH-UHFFFAOYSA-N 6-[4-[(4-chlorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(Cl)=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 LGSSUTQKTCIAEH-UHFFFAOYSA-N 0.000 claims description 2
GSUYTEBFEYLBIG-UHFFFAOYSA-N 6-[4-[(4-cyanophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(=CC=3)C#N)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 GSUYTEBFEYLBIG-UHFFFAOYSA-N 0.000 claims description 2
UUMNSLYUTMORIU-UHFFFAOYSA-N 6-[4-[(6-cyanopyridin-3-yl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=NC(=CC=3)C#N)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 UUMNSLYUTMORIU-UHFFFAOYSA-N 0.000 claims description 2
KRYRAEBYEJXFKK-UHFFFAOYSA-N 6-[4-[[3-[2-(dimethylamino)ethoxy]phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(OCCN(C)C)C=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 KRYRAEBYEJXFKK-UHFFFAOYSA-N 0.000 claims description 2
GGNKYUDFYRCDLO-UHFFFAOYSA-N 6-[4-[[4-(dimethylamino)phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(=CC=3)N(C)C)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 GGNKYUDFYRCDLO-UHFFFAOYSA-N 0.000 claims description 2
GQNYKTYUXWUGPB-UHFFFAOYSA-N 6-[4-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(OCCN(C)C)=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 GQNYKTYUXWUGPB-UHFFFAOYSA-N 0.000 claims description 2
VLNNLIPSTUPDQA-UHFFFAOYSA-N 6-[4-benzyl-5-(2-methylpropyl)-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=C(CC(C)C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 VLNNLIPSTUPDQA-UHFFFAOYSA-N 0.000 claims description 2
BUTVWRKVAOCJSZ-UHFFFAOYSA-N 6-[4-benzyl-5-(methoxymethyl)-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=C(COC)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 BUTVWRKVAOCJSZ-UHFFFAOYSA-N 0.000 claims description 2
FLMWOVLVZWEVFG-UHFFFAOYSA-N 6-[5-methyl-3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound O=C1C(CC=2C=NC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)NC1=CC=CC=C1 FLMWOVLVZWEVFG-UHFFFAOYSA-N 0.000 claims description 2
ALAWGYRXLFPCOW-UHFFFAOYSA-N CC(C(CC1=CC=CN=C1)=C1O)=NN1C(N=C1)=CC=C1S(N1CCCCCC1)(=O)=O Chemical compound CC(C(CC1=CC=CN=C1)=C1O)=NN1C(N=C1)=CC=C1S(N1CCCCCC1)(=O)=O ALAWGYRXLFPCOW-UHFFFAOYSA-N 0.000 claims description 2
206010020772 Hypertension Diseases 0.000 claims description 2
206010053648 Vascular occlusion Diseases 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
230000002490 cerebral effect Effects 0.000 claims description 2
208000029078 coronary artery disease Diseases 0.000 claims description 2
210000002216 heart Anatomy 0.000 claims description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 claims description 2
210000003141 lower extremity Anatomy 0.000 claims description 2
YMCKQWNQPSDJTM-UHFFFAOYSA-N methyl 3-[2-[5-[cyclopentyl(methyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]-3-phenylpropanoate Chemical compound C=1C=CC=CC=1C(CC(=O)OC)C(C1=O)=CNN1C(N=C1)=CC=C1S(=O)(=O)N(C)C1CCCC1 YMCKQWNQPSDJTM-UHFFFAOYSA-N 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
208000010125 myocardial infarction Diseases 0.000 claims description 2
RPYKGSFTNNQOFF-UHFFFAOYSA-N n-cyclopentyl-6-[4-[(4-methoxypyridin-3-yl)methyl]-3-oxo-1h-pyrazol-2-yl]-n-methylpyridine-3-sulfonamide Chemical compound COC1=CC=NC=C1CC(C1=O)=CNN1C1=CC=C(S(=O)(=O)N(C)C2CCCC2)C=N1 RPYKGSFTNNQOFF-UHFFFAOYSA-N 0.000 claims description 2
PLBUFMHWJXZOSI-UHFFFAOYSA-N n-ethyl-6-[3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=NC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 PLBUFMHWJXZOSI-UHFFFAOYSA-N 0.000 claims description 2
UFCONUJXYHROMW-UHFFFAOYSA-N n-ethyl-6-[4-[(2-fluorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=CC=3)F)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 UFCONUJXYHROMW-UHFFFAOYSA-N 0.000 claims description 2
XAYICWFOGXLESY-UHFFFAOYSA-N n-ethyl-6-[4-[(3-hydroxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(O)C=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 XAYICWFOGXLESY-UHFFFAOYSA-N 0.000 claims description 2
CKDHZEVBKHKQQY-UHFFFAOYSA-N n-ethyl-6-[4-[(3-methoxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(OC)C=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 CKDHZEVBKHKQQY-UHFFFAOYSA-N 0.000 claims description 2
PYYDUSCBKZQZLU-UHFFFAOYSA-N n-ethyl-6-[4-[(4-hydroxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(O)=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 PYYDUSCBKZQZLU-UHFFFAOYSA-N 0.000 claims description 2
ZHMMHIFJMKUCOF-UHFFFAOYSA-N n-ethyl-6-[4-[(5-methoxypyridin-3-yl)methyl]-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(OC)C=NC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZHMMHIFJMKUCOF-UHFFFAOYSA-N 0.000 claims description 2
UPVUVUPOMYZAON-UHFFFAOYSA-N n-ethyl-6-[4-[(5-methoxypyridin-3-yl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(OC)C=NC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 UPVUVUPOMYZAON-UHFFFAOYSA-N 0.000 claims description 2
QRWMIMHFYOLUQY-UHFFFAOYSA-N n-ethyl-6-[4-[(6-methoxypyridin-2-yl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3N=C(OC)C=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 QRWMIMHFYOLUQY-UHFFFAOYSA-N 0.000 claims description 2
PZMBTIIMXVDYRL-UHFFFAOYSA-N n-ethyl-6-[4-[[4-(2-methoxyethoxy)phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(OCCOC)=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 PZMBTIIMXVDYRL-UHFFFAOYSA-N 0.000 claims description 2
AEDUJIVKLIHSTQ-UHFFFAOYSA-N n-ethyl-6-[4-[[4-(methoxymethyl)phenyl]methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(COC)=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 AEDUJIVKLIHSTQ-UHFFFAOYSA-N 0.000 claims description 2
SSOYUVJTDWSJIV-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(2-pyridin-2-ylethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CCC=3N=CC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 SSOYUVJTDWSJIV-UHFFFAOYSA-N 0.000 claims description 2
XDPCUYFJKJUGGN-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(pyridin-2-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3N=CC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 XDPCUYFJKJUGGN-UHFFFAOYSA-N 0.000 claims description 2
YWTLJOIJEZFMGL-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(pyridin-4-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CN=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 YWTLJOIJEZFMGL-UHFFFAOYSA-N 0.000 claims description 2
FZZBVGCEVAIDEK-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-[[2-(trifluoromethyl)phenyl]methyl]-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=CC=3)C(F)(F)F)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 FZZBVGCEVAIDEK-UHFFFAOYSA-N 0.000 claims description 2
URTBSJFQFXIMLK-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-[[3-(trifluoromethyl)phenyl]methyl]-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(C=CC=3)C(F)(F)F)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 URTBSJFQFXIMLK-UHFFFAOYSA-N 0.000 claims description 2
WMMNNVDKEUZZLC-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-[[4-(trifluoromethyl)phenyl]methyl]-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(=CC=3)C(F)(F)F)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 WMMNNVDKEUZZLC-UHFFFAOYSA-N 0.000 claims description 2
XJTVXYQCFJEEQO-UHFFFAOYSA-N n-ethyl-6-[5-methyl-4-[(1-methylpiperidin-4-yl)methyl]-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC3CCN(C)CC3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 XJTVXYQCFJEEQO-UHFFFAOYSA-N 0.000 claims description 2
ZGMKEHVMZAIWFI-UHFFFAOYSA-N n-ethyl-6-[5-methyl-4-[(4-methylsulfonylphenyl)methyl]-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=CC(=CC=3)S(C)(=O)=O)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZGMKEHVMZAIWFI-UHFFFAOYSA-N 0.000 claims description 2
DWEVZZAVTHEZIN-UHFFFAOYSA-N n-tert-butyl-6-[4-[(5-methoxypyridin-2-yl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-methylpyridine-3-sulfonamide Chemical compound N1=CC(OC)=CC=C1CC(C1=O)=C(C)NN1C1=CC=C(S(=O)(=O)N(C)C(C)(C)C)C=N1 DWEVZZAVTHEZIN-UHFFFAOYSA-N 0.000 claims description 2
WZAFCFTXMUPKCK-UHFFFAOYSA-N n-tert-butyl-6-[4-[(5-methoxypyridin-3-yl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-methylpyridine-3-sulfonamide Chemical compound COC1=CN=CC(CC=2C(N(C=3N=CC(=CC=3)S(=O)(=O)N(C)C(C)(C)C)NC=2C)=O)=C1 WZAFCFTXMUPKCK-UHFFFAOYSA-N 0.000 claims description 2
230000036961 partial effect Effects 0.000 claims description 2
230000002093 peripheral effect Effects 0.000 claims description 2
208000002815 pulmonary hypertension Diseases 0.000 claims description 2
230000001172 regenerating effect Effects 0.000 claims description 2
208000021331 vascular occlusion disease Diseases 0.000 claims description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 2
ZFRDUXKCJKFEEO-UHFFFAOYSA-N 2-[4-benzyl-2-[5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl]-3-oxo-1h-pyrazol-5-yl]-n,n-dimethylacetamide Chemical compound C=1C=C(N2C(C(CC=3C=CC=CC=3)=C(CC(=O)N(C)C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZFRDUXKCJKFEEO-UHFFFAOYSA-N 0.000 claims 1
KELSKVJIIQTLRV-UHFFFAOYSA-N 2-[5-(trifluoromethyl)pyridin-2-yl]-1h-pyrazol-5-one Chemical compound N1=C(O)C=CN1C1=CC=C(C(F)(F)F)C=N1 KELSKVJIIQTLRV-UHFFFAOYSA-N 0.000 claims 1
TWADPCAXZGNFBV-IYBDPMFKSA-N 2-[5-[(3s,5r)-3,5-dimethylpiperidin-1-yl]sulfonylpyridin-2-yl]-4-[(2-fluorophenyl)methyl]-5-methyl-1h-pyrazol-3-one Chemical compound C1[C@@H](C)C[C@@H](C)CN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C(=CC=CC=3)F)=C(C)N2)=O)N=C1 TWADPCAXZGNFBV-IYBDPMFKSA-N 0.000 claims 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
ZMZDWLCXZNPBBU-GASCZTMLSA-N 4-[(2-chloro-6-fluorophenyl)methyl]-2-[5-[(3s,5r)-3,5-dimethylpiperidin-1-yl]sulfonylpyridin-2-yl]-5-methyl-1h-pyrazol-3-one Chemical compound C1[C@@H](C)C[C@@H](C)CN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C(=CC=CC=3F)Cl)=C(C)N2)=O)N=C1 ZMZDWLCXZNPBBU-GASCZTMLSA-N 0.000 claims 1
UXACXPAQXUULGO-IYBDPMFKSA-N 4-[(4-chlorophenyl)methyl]-2-[5-[(3s,5r)-3,5-dimethylpiperidin-1-yl]sulfonylpyridin-2-yl]-5-methyl-1h-pyrazol-3-one Chemical compound C1[C@@H](C)C[C@@H](C)CN1S(=O)(=O)C1=CC=C(N2C(C(CC=3C=CC(Cl)=CC=3)=C(C)N2)=O)N=C1 UXACXPAQXUULGO-IYBDPMFKSA-N 0.000 claims 1
KNZXSSVRYAVIKK-UHFFFAOYSA-N 4-[[3-(2-methoxyethoxy)phenyl]methyl]-5-methyl-2-pyridin-2-yl-1h-pyrazol-3-one Chemical compound COCCOC1=CC=CC(CC=2C(N(C=3N=CC=CC=3)NC=2C)=O)=C1 KNZXSSVRYAVIKK-UHFFFAOYSA-N 0.000 claims 1
ZBTHCJYPEYCYDL-UHFFFAOYSA-N ethyl 2-[4-benzyl-2-[5-[ethyl(phenyl)sulfamoyl]pyridin-2-yl]-3-oxo-1H-pyrazol-5-yl]acetate Chemical compound O=C1C(CC=2C=CC=CC=2)=C(CC(=O)OCC)NN1C(N=C1)=CC=C1S(=O)(=O)N(CC)C1=CC=CC=C1 ZBTHCJYPEYCYDL-UHFFFAOYSA-N 0.000 claims 1
LVNFNSROGYZPSO-UHFFFAOYSA-N ethyl 3-[2-[5-(tert-butylsulfamoyl)pyridin-2-yl]-3-oxo-1h-pyrazol-4-yl]-3-phenylpropanoate Chemical compound C=1C=CC=CC=1C(CC(=O)OCC)C(C1=O)=CNN1C1=CC=C(S(=O)(=O)NC(C)(C)C)C=N1 LVNFNSROGYZPSO-UHFFFAOYSA-N 0.000 claims 1
PDXWWXBNAKOXKK-UHFFFAOYSA-N n-(2,3-dihydroxypropyl)-6-[3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide;hydrochloride Chemical compound Cl.C=1C=C(N2C(C(CC=3C=NC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CC(O)CO)C1=CC=CC=C1 PDXWWXBNAKOXKK-UHFFFAOYSA-N 0.000 claims 1
KASMCQONCDSIAN-UHFFFAOYSA-N n-ethyl-6-[4-[(2-methoxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C(=CC=CC=3)OC)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 KASMCQONCDSIAN-UHFFFAOYSA-N 0.000 claims 1
230000007170 pathology Effects 0.000 claims 1
210000000130 stem cell Anatomy 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 132
238000005160 1H NMR spectroscopy Methods 0.000 description 102
230000002829 reductive effect Effects 0.000 description 86
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 82
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
239000000203 mixture Substances 0.000 description 73
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
239000007832 Na2SO4 Substances 0.000 description 68
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 68
229910052938 sodium sulfate Inorganic materials 0.000 description 68
235000011152 sodium sulphate Nutrition 0.000 description 68
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
210000004027 cell Anatomy 0.000 description 62
239000002609 medium Substances 0.000 description 62
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical group CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 49
239000000243 solution Substances 0.000 description 49
229910001868 water Inorganic materials 0.000 description 46
239000000843 powder Substances 0.000 description 40
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
239000003921 oil Substances 0.000 description 37
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
238000010898 silica gel chromatography Methods 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical group C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 27
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
125000000753 cycloalkyl group Chemical group 0.000 description 26
238000003756 stirring Methods 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
102100028471 Eosinophil peroxidase Human genes 0.000 description 25
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
108090000623 proteins and genes Proteins 0.000 description 24
239000007787 solid Substances 0.000 description 24
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 23
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 23
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
239000012429 reaction media Substances 0.000 description 19
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 17
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 16
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
239000012074 organic phase Substances 0.000 description 16
102000004169 proteins and genes Human genes 0.000 description 16
235000017557 sodium bicarbonate Nutrition 0.000 description 16
229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
239000011780 sodium chloride Substances 0.000 description 16
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 16
239000002585 base Substances 0.000 description 15
239000000499 gel Substances 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 14
VTUBMCBPPGZPTD-UHFFFAOYSA-N n-ethyl-6-hydrazinyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(NN)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 VTUBMCBPPGZPTD-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
229910052786 argon Inorganic materials 0.000 description 13
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 13
244000257039 Duranta repens Species 0.000 description 12
206010021143 Hypoxia Diseases 0.000 description 12
230000007954 hypoxia Effects 0.000 description 12
238000005259 measurement Methods 0.000 description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 12
241000238366 Cephalopoda Species 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
238000003556 assay Methods 0.000 description 10
239000011734 sodium Substances 0.000 description 10
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
241001466077 Salina Species 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 9
150000001721 carbon Chemical group 0.000 description 9
BEEJALPUCUEZOU-UHFFFAOYSA-N methyl 2-benzyl-3-oxopropanoate Chemical compound COC(=O)C(C=O)CC1=CC=CC=C1 BEEJALPUCUEZOU-UHFFFAOYSA-N 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
229910052708 sodium Inorganic materials 0.000 description 9
150000003456 sulfonamides Chemical class 0.000 description 9
QXZKKHONVQGXAK-UHFFFAOYSA-N 6-chloropyridine-3-sulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=N1 QXZKKHONVQGXAK-UHFFFAOYSA-N 0.000 description 8
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
108091023040 Transcription factor Proteins 0.000 description 8
102000040945 Transcription factor Human genes 0.000 description 8
102000005936 beta-Galactosidase Human genes 0.000 description 8
108010005774 beta-Galactosidase Proteins 0.000 description 8
229910052796 boron Inorganic materials 0.000 description 8
230000007959 normoxia Effects 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
235000015320 potassium carbonate Nutrition 0.000 description 8
239000012047 saturated solution Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
241000282412 Homo Species 0.000 description 7
241001465754 Metazoa Species 0.000 description 7
229910000024 caesium carbonate Inorganic materials 0.000 description 7
230000000694 effects Effects 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
238000010992 reflux Methods 0.000 description 7
PTLZUYYTWMVUEN-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxan-5-yl)methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1COC(C)(C)OC1 PTLZUYYTWMVUEN-UHFFFAOYSA-N 0.000 description 6
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 6
108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000012230 colorless oil Substances 0.000 description 6
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
238000010790 dilution Methods 0.000 description 6
239000012895 dilution Substances 0.000 description 6
108010018033 endothelial PAS domain-containing protein 1 Proteins 0.000 description 6
NEXGNHZJZRNAPF-UHFFFAOYSA-N n-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]cyclopentanamine Chemical compound C1OC(C)(C)OCC1CNC1CCCC1 NEXGNHZJZRNAPF-UHFFFAOYSA-N 0.000 description 6
239000003586 protic polar solvent Substances 0.000 description 6
150000003254 radicals Chemical class 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
235000005074 zinc chloride Nutrition 0.000 description 6
239000011592 zinc chloride Substances 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
108020004566 Transfer RNA Proteins 0.000 description 5
230000003213 activating effect Effects 0.000 description 5
125000002947 alkylene group Chemical group 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-UHFFFAOYSA-N 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 5
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000012634 fragment Substances 0.000 description 5
239000001963 growth medium Substances 0.000 description 5
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 5
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 5
230000004044 response Effects 0.000 description 5
235000009518 sodium iodide Nutrition 0.000 description 5
230000006641 stabilisation Effects 0.000 description 5
238000011105 stabilization Methods 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 4
LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 4
101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 4
239000012317 TBTU Substances 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000004913 activation Effects 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
229960000958 deferoxamine Drugs 0.000 description 4
WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 4
XVARCVCWNFACQC-RKQHYHRCSA-N indican Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=CC=C12 XVARCVCWNFACQC-RKQHYHRCSA-N 0.000 description 4
238000007918 intramuscular administration Methods 0.000 description 4
BXIZABBXFTVLDS-UHFFFAOYSA-N methyl 3-oxo-2-(pyridin-3-ylmethyl)butanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=CN=C1 BXIZABBXFTVLDS-UHFFFAOYSA-N 0.000 description 4
UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 4
DCPGLWKMMPRIHG-UHFFFAOYSA-N n-cyclopentyl-n-[(2,2-dimethyl-1,3-dioxan-5-yl)methyl]-6-hydrazinylpyridine-3-sulfonamide Chemical compound C1OC(C)(C)OCC1CN(S(=O)(=O)C=1C=NC(NN)=CC=1)C1CCCC1 DCPGLWKMMPRIHG-UHFFFAOYSA-N 0.000 description 4
229910000489 osmium tetroxide Inorganic materials 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
239000000047 product Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000006228 supernatant Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
239000013598 vector Substances 0.000 description 4
GYOWJXLULJKXML-JHEYCYPBSA-N (1r,3s)-3-(phenylmethoxymethyl)cyclopentan-1-amine;hydrochloride Chemical compound Cl.C1[C@H](N)CC[C@@H]1COCC1=CC=CC=C1 GYOWJXLULJKXML-JHEYCYPBSA-N 0.000 description 3
WDVDHJLKXYCOFS-UHFFFAOYSA-N (5-bromopyridin-3-yl)methanol Chemical compound OCC1=CN=CC(Br)=C1 WDVDHJLKXYCOFS-UHFFFAOYSA-N 0.000 description 3
XVTRFVQEOUESFM-UHFFFAOYSA-N 1-(bromomethyl)-3-(2-methoxyethoxy)benzene Chemical compound COCCOC1=CC=CC(CBr)=C1 XVTRFVQEOUESFM-UHFFFAOYSA-N 0.000 description 3
BMGVAPLBALXXEC-UHFFFAOYSA-N 1-(bromomethyl)-3-(methoxymethyl)benzene Chemical compound COCC1=CC=CC(CBr)=C1 BMGVAPLBALXXEC-UHFFFAOYSA-N 0.000 description 3
RAMMQILXXBBYAY-UHFFFAOYSA-N 2,2-dimethylpropyl 6-chloropyridine-3-carboxylate Chemical compound CC(C)(C)COC(=O)C1=CC=C(Cl)N=C1 RAMMQILXXBBYAY-UHFFFAOYSA-N 0.000 description 3
LVFFZQQWIZURIO-MRVPVSSYSA-N 2-Phenylsuccinic acid Chemical compound OC(=O)C[C@@H](C(O)=O)C1=CC=CC=C1 LVFFZQQWIZURIO-MRVPVSSYSA-N 0.000 description 3
ZFXKYWKSLGJAPI-UHFFFAOYSA-N 2-chloro-5-phenylsulfanylpyridine Chemical compound C1=NC(Cl)=CC=C1SC1=CC=CC=C1 ZFXKYWKSLGJAPI-UHFFFAOYSA-N 0.000 description 3
ZWXVKOBPKVFJOT-UHFFFAOYSA-N 4-ethoxy-3-formyl-4-oxobutanoic acid Chemical compound CCOC(=O)C(C=O)CC(O)=O ZWXVKOBPKVFJOT-UHFFFAOYSA-N 0.000 description 3
VLBYFPORMIPFHE-UHFFFAOYSA-N 5-(benzenesulfonyl)-2-chloropyridine Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)C1=CC=CC=C1 VLBYFPORMIPFHE-UHFFFAOYSA-N 0.000 description 3
XHUTYLPZWIBCIZ-UHFFFAOYSA-N 5-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=CN=CC(C#N)=C1 XHUTYLPZWIBCIZ-UHFFFAOYSA-N 0.000 description 3
MNMDVGJZONSKMO-UHFFFAOYSA-N 5-(hydroxymethyl)pyridine-3-carbonitrile Chemical compound OCC1=CN=CC(C#N)=C1 MNMDVGJZONSKMO-UHFFFAOYSA-N 0.000 description 3
NUDKOTFTXVFFBH-UKILVPOCSA-N 6-(4-benzyl-3-oxo-1h-pyrazol-2-yl)-n-[(1r,3s)-3-(phenylmethoxymethyl)cyclopentyl]pyridine-3-sulfonamide Chemical compound C=1NN(C=2N=CC(=CC=2)S(=O)(=O)N[C@H]2C[C@@H](COCC=3C=CC=CC=3)CC2)C(=O)C=1CC1=CC=CC=C1 NUDKOTFTXVFFBH-UKILVPOCSA-N 0.000 description 3
ZKZTULWHDVRRJY-UHFFFAOYSA-N 6-chloro-n,n-dimethylpyridine-3-sulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)N=C1 ZKZTULWHDVRRJY-UHFFFAOYSA-N 0.000 description 3
NCXUILGLMMKECM-UHFFFAOYSA-N 6-chloro-n-(2,3-dihydroxypropyl)-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(Cl)N=CC=1S(=O)(=O)N(CC(O)CO)C1=CC=CC=C1 NCXUILGLMMKECM-UHFFFAOYSA-N 0.000 description 3
LUPHWLFPAYCSCK-JKSUJKDBSA-N 6-chloro-n-[(1r,3s)-3-(phenylmethoxymethyl)cyclopentyl]pyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)N[C@H]1C[C@@H](COCC=2C=CC=CC=2)CC1 LUPHWLFPAYCSCK-JKSUJKDBSA-N 0.000 description 3
MRVPLKXXLCTZST-UHFFFAOYSA-N 6-chloro-n-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-n-phenylpyridine-3-sulfonamide Chemical compound O1C(C)(C)OCC1CN(S(=O)(=O)C=1C=NC(Cl)=CC=1)C1=CC=CC=C1 MRVPLKXXLCTZST-UHFFFAOYSA-N 0.000 description 3
BQAWNMWPJQPUMG-UHFFFAOYSA-N 6-chloro-n-cyclopentyl-n-(3-phenylmethoxypropyl)pyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)N(C1CCCC1)CCCOCC1=CC=CC=C1 BQAWNMWPJQPUMG-UHFFFAOYSA-N 0.000 description 3
PKHSAJUKYDRFHN-UHFFFAOYSA-N 6-chloro-n-cyclopentylpyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)NC1CCCC1 PKHSAJUKYDRFHN-UHFFFAOYSA-N 0.000 description 3
FAZWOTCKCLETLD-UHFFFAOYSA-N 6-chloro-n-phenyl-n-prop-2-enylpyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)N(CC=C)C1=CC=CC=C1 FAZWOTCKCLETLD-UHFFFAOYSA-N 0.000 description 3
RHAXQCFTVKAOSS-UHFFFAOYSA-N 6-chloro-n-phenylpyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)NC1=CC=CC=C1 RHAXQCFTVKAOSS-UHFFFAOYSA-N 0.000 description 3
GYHBVHHXVVZKJL-UHFFFAOYSA-N 6-hydrazinyl-n,n-dimethylpyridine-3-sulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(NN)N=C1 GYHBVHHXVVZKJL-UHFFFAOYSA-N 0.000 description 3
GNZQOSOGJMMPCK-DLBZAZTESA-N 6-hydrazinyl-n-methyl-n-[(1r,3s)-3-(phenylmethoxymethyl)cyclopentyl]pyridine-3-sulfonamide Chemical compound C([C@H]1CC[C@H](C1)N(C)S(=O)(=O)C=1C=NC(NN)=CC=1)OCC1=CC=CC=C1 GNZQOSOGJMMPCK-DLBZAZTESA-N 0.000 description 3
102100030907 Aryl hydrocarbon receptor nuclear translocator Human genes 0.000 description 3
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 3
101000690445 Caenorhabditis elegans Aryl hydrocarbon receptor nuclear translocator homolog Proteins 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
238000002965 ELISA Methods 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
241000282414 Homo sapiens Species 0.000 description 3
101000793115 Homo sapiens Aryl hydrocarbon receptor nuclear translocator Proteins 0.000 description 3
OHRLCOYXQMMTIX-UHFFFAOYSA-N N1=NC(C=C1)=O.FC(C(=O)O)(F)F Chemical compound N1=NC(C=C1)=O.FC(C(=O)O)(F)F OHRLCOYXQMMTIX-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 3
108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
108090000848 Ubiquitin Proteins 0.000 description 3
102000044159 Ubiquitin Human genes 0.000 description 3
VHVHEJJCAWUWBA-UHFFFAOYSA-N [5-(benzenesulfonyl)pyridin-2-yl]hydrazine Chemical compound C1=NC(NN)=CC=C1S(=O)(=O)C1=CC=CC=C1 VHVHEJJCAWUWBA-UHFFFAOYSA-N 0.000 description 3
230000006978 adaptation Effects 0.000 description 3
TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
230000027455 binding Effects 0.000 description 3
238000009739 binding Methods 0.000 description 3
239000012267 brine Substances 0.000 description 3
125000005587 carbonate group Chemical group 0.000 description 3
230000015556 catabolic process Effects 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 3
238000006731 degradation reaction Methods 0.000 description 3
HZOCADZQLFGJLU-UHFFFAOYSA-N diethyl 2-benzyl-3-oxopentanedioate Chemical compound CCOC(=O)CC(=O)C(C(=O)OCC)CC1=CC=CC=C1 HZOCADZQLFGJLU-UHFFFAOYSA-N 0.000 description 3
FRMAATUMCKYMEG-UHFFFAOYSA-N diethyl 2-formyl-3-phenylbutanedioate Chemical compound CCOC(=O)C(C=O)C(C(=O)OCC)C1=CC=CC=C1 FRMAATUMCKYMEG-UHFFFAOYSA-N 0.000 description 3
QMDIQXCKFVLQRH-UHFFFAOYSA-N diethyl 2-formyl-3-phenylpentanedioate Chemical compound CCOC(=O)CC(C(C=O)C(=O)OCC)C1=CC=CC=C1 QMDIQXCKFVLQRH-UHFFFAOYSA-N 0.000 description 3
JVQDNCKPHSZFSO-UHFFFAOYSA-N diethyl 2-phenylbutanedioate Chemical compound CCOC(=O)CC(C(=O)OCC)C1=CC=CC=C1 JVQDNCKPHSZFSO-UHFFFAOYSA-N 0.000 description 3
GSDRMAHJAKQAOZ-UHFFFAOYSA-N diethyl 3-phenylpentanedioate Chemical compound CCOC(=O)CC(CC(=O)OCC)C1=CC=CC=C1 GSDRMAHJAKQAOZ-UHFFFAOYSA-N 0.000 description 3
239000003480 eluent Substances 0.000 description 3
HJKJXWMIISKYGB-UHFFFAOYSA-N ethyl 3-cyano-3-phenylpropanoate Chemical compound CCOC(=O)CC(C#N)C1=CC=CC=C1 HJKJXWMIISKYGB-UHFFFAOYSA-N 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
238000004020 luminiscence type Methods 0.000 description 3
239000012139 lysis buffer Substances 0.000 description 3
YCIPYKWVVFJTFZ-UHFFFAOYSA-N methyl 2-[(6-chloropyridin-3-yl)sulfonyl-cyclopentylamino]acetate Chemical compound C=1C=C(Cl)N=CC=1S(=O)(=O)N(CC(=O)OC)C1CCCC1 YCIPYKWVVFJTFZ-UHFFFAOYSA-N 0.000 description 3
NYECVDPYRMZGGT-UHFFFAOYSA-N methyl 2-[[3-(methoxymethyl)phenyl]methyl]-3-oxobutanoate Chemical compound COCC1=CC=CC(CC(C(C)=O)C(=O)OC)=C1 NYECVDPYRMZGGT-UHFFFAOYSA-N 0.000 description 3
VZNMTXJDYBAROC-UHFFFAOYSA-N methyl 2-[[3-[2-(dimethylamino)ethoxy]phenyl]methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=CC(OCCN(C)C)=C1 VZNMTXJDYBAROC-UHFFFAOYSA-N 0.000 description 3
DUKKMFOQZGUKBY-UHFFFAOYSA-N methyl 2-acetyl-3-methyl-3-phenylbutanoate Chemical compound COC(=O)C(C(C)=O)C(C)(C)C1=CC=CC=C1 DUKKMFOQZGUKBY-UHFFFAOYSA-N 0.000 description 3
CDHWLGSCWGPPCT-UHFFFAOYSA-N methyl 2-acetyl-3-methylbut-2-enoate Chemical compound COC(=O)C(=C(C)C)C(C)=O CDHWLGSCWGPPCT-UHFFFAOYSA-N 0.000 description 3
YFWRYDDXFJXORP-UHFFFAOYSA-N methyl 2-acetyl-3-phenylbut-3-enoate Chemical compound COC(=O)C(C(C)=O)C(=C)C1=CC=CC=C1 YFWRYDDXFJXORP-UHFFFAOYSA-N 0.000 description 3
DNRHHRLMLKBSEW-UHFFFAOYSA-N methyl 2-benzyl-4,4,4-trifluoro-3,3-dihydroxybutanoate Chemical compound COC(=O)C(C(O)(O)C(F)(F)F)CC1=CC=CC=C1 DNRHHRLMLKBSEW-UHFFFAOYSA-N 0.000 description 3
POCCTEWXDVNHGU-UHFFFAOYSA-N methyl 3-oxo-2-(1-phenylcyclopropyl)butanoate Chemical compound C=1C=CC=CC=1C1(C(C(C)=O)C(=O)OC)CC1 POCCTEWXDVNHGU-UHFFFAOYSA-N 0.000 description 3
JFJGEFXEJIIBIO-UHFFFAOYSA-N n-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-6-hydrazinyl-n-phenylpyridine-3-sulfonamide Chemical compound O1C(C)(C)OCC1CN(S(=O)(=O)C=1C=NC(NN)=CC=1)C1=CC=CC=C1 JFJGEFXEJIIBIO-UHFFFAOYSA-N 0.000 description 3
IMOXXBWDLRALIO-UHFFFAOYSA-N n-tert-butyl-6-chloropyridine-3-sulfonamide Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=C(Cl)N=C1 IMOXXBWDLRALIO-UHFFFAOYSA-N 0.000 description 3
LQOXAYWRWICCEN-UHFFFAOYSA-N n-tert-butyl-6-hydrazinylpyridine-3-sulfonamide Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=C(NN)N=C1 LQOXAYWRWICCEN-UHFFFAOYSA-N 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
230000000704 physical effect Effects 0.000 description 3
150000003148 prolines Chemical class 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
235000011149 sulphuric acid Nutrition 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 3
BTAUZIVCHJIXAX-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxan-5-yl)methanol Chemical compound CC1(C)OCC(CO)CO1 BTAUZIVCHJIXAX-UHFFFAOYSA-N 0.000 description 2
MIAKOEWBCMPCQR-YBXAARCKSA-N (2s,3r,4s,5r,6r)-2-(4-aminophenoxy)-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound C1=CC(N)=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MIAKOEWBCMPCQR-YBXAARCKSA-N 0.000 description 2
KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 2
IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
OKVJCVWFVRATSG-UHFFFAOYSA-N 3-hydroxybenzyl alcohol Chemical compound OCC1=CC=CC(O)=C1 OKVJCVWFVRATSG-UHFFFAOYSA-N 0.000 description 2
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
KNUKSVHXGMRLBQ-UHFFFAOYSA-N 6-(4-benzyl-3-oxo-5-propyl-1h-pyrazol-2-yl)-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound O=C1C(CC=2C=CC=CC=2)=C(CCC)NN1C(N=C1)=CC=C1S(=O)(=O)N(CC)C1=CC=CC=C1 KNUKSVHXGMRLBQ-UHFFFAOYSA-N 0.000 description 2
QQESMQFOJMVDPS-DLBZAZTESA-N 6-chloro-n-methyl-n-[(1r,3s)-3-(phenylmethoxymethyl)cyclopentyl]pyridine-3-sulfonamide Chemical compound C([C@H]1CC[C@H](C1)N(C)S(=O)(=O)C=1C=NC(Cl)=CC=1)OCC1=CC=CC=C1 QQESMQFOJMVDPS-DLBZAZTESA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
IYVGZNRBHURABX-UHFFFAOYSA-N C=1C=C(N2C(C(C(CC(O)=O)C=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(C)C1CCCC1 Chemical compound C=1C=C(N2C(C(C(CC(O)=O)C=3C=CC=CC=3)=CN2)=O)N=CC=1S(=O)(=O)N(C)C1CCCC1 IYVGZNRBHURABX-UHFFFAOYSA-N 0.000 description 2
PLYQXHYYSFPDBV-UHFFFAOYSA-N CC(C)(C)NS(C1=CC=C(N2N=CC(C(C(O)=O)C3=CC=CC=C3)=C2O)N=C1)(=O)=O Chemical compound CC(C)(C)NS(C1=CC=C(N2N=CC(C(C(O)=O)C3=CC=CC=C3)=C2O)N=C1)(=O)=O PLYQXHYYSFPDBV-UHFFFAOYSA-N 0.000 description 2
201000009030 Carcinoma Diseases 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
101100393884 Drosophila melanogaster Glut1 gene Proteins 0.000 description 2
101150002621 EPO gene Proteins 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
ZDXPYRJPNDTMRX-UHFFFAOYSA-N Glutamine Chemical compound OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
102000004079 Prolyl Hydroxylases Human genes 0.000 description 2
108010043005 Prolyl Hydroxylases Proteins 0.000 description 2
240000001987 Pyrus communis Species 0.000 description 2
108091006296 SLC2A1 Proteins 0.000 description 2
101150058068 SLC2A1 gene Proteins 0.000 description 2
101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 2
101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
BEUUKQVMESPVDK-UHFFFAOYSA-N [3-(2-methoxyethoxy)phenyl]methanol Chemical compound COCCOC1=CC=CC(CO)=C1 BEUUKQVMESPVDK-UHFFFAOYSA-N 0.000 description 2
LCRNBZWULOCFRL-UHFFFAOYSA-N [3-(methoxymethyl)phenyl]methanol Chemical compound COCC1=CC=CC(CO)=C1 LCRNBZWULOCFRL-UHFFFAOYSA-N 0.000 description 2
DZFBVULFUPHSOS-UHFFFAOYSA-N ac1mpfs7 Chemical group C1=C(OC)C(OC)=CC=C1CCNC1=NC=NC2=C1SC1=NC(N3CCOCC3)=C(COC(C)(C)C3)C3=C21 DZFBVULFUPHSOS-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
230000033228 biological regulation Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000003245 coal Substances 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
238000001514 detection method Methods 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
238000009826 distribution Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 2
KYUPGXAAKZLYIL-UHFFFAOYSA-N ethyl 2-benzyl-3-oxohexanoate Chemical compound CCCC(=O)C(C(=O)OCC)CC1=CC=CC=C1 KYUPGXAAKZLYIL-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
210000003494 hepatocyte Anatomy 0.000 description 2
239000000833 heterodimer Substances 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
230000033444 hydroxylation Effects 0.000 description 2
238000005805 hydroxylation reaction Methods 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
BXFFHSIDQOFMLE-UHFFFAOYSA-N indoxyl sulfate Natural products C1=CC=C2C(OS(=O)(=O)O)=CNC2=C1 BXFFHSIDQOFMLE-UHFFFAOYSA-N 0.000 description 2
XVARCVCWNFACQC-UHFFFAOYSA-N indoxyl-beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CNC2=CC=CC=C12 XVARCVCWNFACQC-UHFFFAOYSA-N 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
230000009021 linear effect Effects 0.000 description 2
239000006166 lysate Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
DSQQFAYQCSFWSM-UHFFFAOYSA-N methyl 2-[(4-aminophenyl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=C(N)C=C1 DSQQFAYQCSFWSM-UHFFFAOYSA-N 0.000 description 2
RYLCDCFJRTXQPZ-UHFFFAOYSA-N methyl 2-[(4-methoxyphenyl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=C(OC)C=C1 RYLCDCFJRTXQPZ-UHFFFAOYSA-N 0.000 description 2
IZSSLIJJSCJRHL-UHFFFAOYSA-N methyl 2-[[4-(dimethylamino)phenyl]methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=C(N(C)C)C=C1 IZSSLIJJSCJRHL-UHFFFAOYSA-N 0.000 description 2
BVOZQEVGTGCECC-UHFFFAOYSA-N methyl 2-formyl-3-(5-methoxypyridin-3-yl)propanoate Chemical compound COC(=O)C(C=O)CC1=CN=CC(OC)=C1 BVOZQEVGTGCECC-UHFFFAOYSA-N 0.000 description 2
PZQUFVGWJHJWNZ-UHFFFAOYSA-N methyl 2-formyl-3-pyridin-3-ylpropanoate Chemical compound COC(=O)C(C=O)CC1=CC=CN=C1 PZQUFVGWJHJWNZ-UHFFFAOYSA-N 0.000 description 2
XPIWVCAMONZQCP-UHFFFAOYSA-N methyl 2-oxobutanoate Chemical compound CCC(=O)C(=O)OC XPIWVCAMONZQCP-UHFFFAOYSA-N 0.000 description 2
QRWOJCWXAATKHF-UHFFFAOYSA-N methyl 3-(5-methoxypyridin-3-yl)propanoate Chemical compound COC(=O)CCC1=CN=CC(OC)=C1 QRWOJCWXAATKHF-UHFFFAOYSA-N 0.000 description 2
QKBHEZBYHDVOTM-UHFFFAOYSA-N methyl 3-(methoxymethyl)benzoate Chemical compound COCC1=CC=CC(C(=O)OC)=C1 QKBHEZBYHDVOTM-UHFFFAOYSA-N 0.000 description 2
RPUSRLKKXPQSGP-UHFFFAOYSA-N methyl 3-phenylpropanoate Chemical compound COC(=O)CCC1=CC=CC=C1 RPUSRLKKXPQSGP-UHFFFAOYSA-N 0.000 description 2
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
PFBFJGMWDWUBBV-UHFFFAOYSA-N n-cyclopentyl-6-hydrazinyl-n-(3-phenylmethoxypropyl)pyridine-3-sulfonamide Chemical compound C1=NC(NN)=CC=C1S(=O)(=O)N(C1CCCC1)CCCOCC1=CC=CC=C1 PFBFJGMWDWUBBV-UHFFFAOYSA-N 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229940072033 potash Drugs 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
230000028327 secretion Effects 0.000 description 2
238000011896 sensitive detection Methods 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
239000012453 solvate Substances 0.000 description 2
238000009331 sowing Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000003826 tablet Substances 0.000 description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 2
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
230000002103 transcriptional effect Effects 0.000 description 2
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
238000001262 western blot Methods 0.000 description 2
RNJQBGXOSAQQDG-JGVFFNPUSA-N (1s,3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)N[C@@H]1CC[C@H](C(O)=O)C1 RNJQBGXOSAQQDG-JGVFFNPUSA-N 0.000 description 1
PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 description 1
NTMYVTSWQJFCPA-UHFFFAOYSA-N (2-tert-butylpyrimidin-5-yl)oxy-ethoxy-propan-2-yloxy-sulfanylidene-$l^{5}-phosphane;[cyano-(4-fluoro-3-phenoxyphenyl)methyl] 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate Chemical compound CCOP(=S)(OC(C)C)OC1=CN=C(C(C)(C)C)N=C1.CC1(C)C(C=C(Cl)Cl)C1C(=O)OC(C#N)C1=CC=C(F)C(OC=2C=CC=CC=2)=C1 NTMYVTSWQJFCPA-UHFFFAOYSA-N 0.000 description 1
QGVJJXJRGYQAST-UHFFFAOYSA-N 1,2-bis(2-methylphenyl)ethane-1,2-dione Chemical compound CC1=CC=CC=C1C(=O)C(=O)C1=CC=CC=C1C QGVJJXJRGYQAST-UHFFFAOYSA-N 0.000 description 1
MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
BNBHZSAKYATYKB-UHFFFAOYSA-N 2,2-dimethylpropyl 6-hydrazinylpyridine-3-carboxylate Chemical compound CC(C)(C)COC(=O)C1=CC=C(NN)N=C1 BNBHZSAKYATYKB-UHFFFAOYSA-N 0.000 description 1
GRMKVJPEYUVDIP-UHFFFAOYSA-N 2,5-dimethoxy-n-[1-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)cyclohexyl]benzenesulfonamide Chemical group COC1=CC=C(OC)C(S(=O)(=O)NC2(CCCCC2)C=2ON=C(N=2)C=2C=NC=CC=2)=C1 GRMKVJPEYUVDIP-UHFFFAOYSA-N 0.000 description 1
VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 description 1
QILFCHBHNJONDS-UHFFFAOYSA-N 2-[5-(4-benzylpiperidin-1-yl)sulfonylpyridin-2-yl]-5-methyl-4-(pyridin-3-ylmethyl)-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C=NC=CC=2)=C(C)NN1C(N=C1)=CC=C1S(=O)(=O)N(CC1)CCC1CC1=CC=CC=C1 QILFCHBHNJONDS-UHFFFAOYSA-N 0.000 description 1
PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 1
QWLGCWXSNYKKDO-UHFFFAOYSA-N 2-chloro-5-iodopyridine Chemical compound ClC1=CC=C(I)C=N1 QWLGCWXSNYKKDO-UHFFFAOYSA-N 0.000 description 1
LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
FZIABZQRRYQFBB-UHFFFAOYSA-N 2-phenylpyridine-3-sulfonamide Chemical compound NS(=O)(=O)C1=CC=CN=C1C1=CC=CC=C1 FZIABZQRRYQFBB-UHFFFAOYSA-N 0.000 description 1
UAPKLGLVGBGMRA-UHFFFAOYSA-N 2-pyridin-2-yl-1h-pyrazol-5-one Chemical compound N1C(=O)C=CN1C1=CC=CC=N1 UAPKLGLVGBGMRA-UHFFFAOYSA-N 0.000 description 1
KSNKQSPJFRQSEI-UHFFFAOYSA-M 3,3,3-trifluoropropanoate Chemical compound [O-]C(=O)CC(F)(F)F KSNKQSPJFRQSEI-UHFFFAOYSA-M 0.000 description 1
WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
CZGUSIXMZVURDU-UHFFFAOYSA-N 3-azaniumyl-4-[[1-[[1-[[1-[[1-[[1-[2-[(1-carboxylato-2-phenylethyl)carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-(diam Chemical compound C=1N=CNC=1CC(C(=O)N1C(CCC1)C(=O)NC(CC=1C=CC=CC=1)C(O)=O)NC(=O)C(C(C)CC)NC(=O)C(NC(=O)C(NC(=O)C(CCCN=C(N)N)NC(=O)C(N)CC(O)=O)C(C)C)CC1=CC=C(O)C=C1 CZGUSIXMZVURDU-UHFFFAOYSA-N 0.000 description 1
PSUXTZLDBVEZTD-UHFFFAOYSA-N 3-bromopropoxymethylbenzene Chemical compound BrCCCOCC1=CC=CC=C1 PSUXTZLDBVEZTD-UHFFFAOYSA-N 0.000 description 1
NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
RZOKZOYSUCSPDF-UHFFFAOYSA-N 3-phenylpentanedioic acid Chemical compound OC(=O)CC(CC(O)=O)C1=CC=CC=C1 RZOKZOYSUCSPDF-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
LOLKAJARZKDJTD-UHFFFAOYSA-N 4-Ethoxy-4-oxobutanoic acid Chemical compound CCOC(=O)CCC(O)=O LOLKAJARZKDJTD-UHFFFAOYSA-N 0.000 description 1
ITZRTTFJMAELQW-UHFFFAOYSA-N 4-[(2,4-dichlorophenyl)methyl]-5-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]-1h-pyrazol-3-one Chemical compound O=C1C(CC=2C(=CC(Cl)=CC=2)Cl)=C(C)NN1C1=CC=C(C(F)(F)F)C=N1 ITZRTTFJMAELQW-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
FQIUCPGDKPXSLL-UHFFFAOYSA-N 5-bromopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(Br)=C1 FQIUCPGDKPXSLL-UHFFFAOYSA-N 0.000 description 1
YOVIXSRXKCZJRN-UHFFFAOYSA-N 5-methoxypyridine-3-carbaldehyde Chemical compound COC1=CN=CC(C=O)=C1 YOVIXSRXKCZJRN-UHFFFAOYSA-N 0.000 description 1
KQEOSIGOXSGWBG-UHFFFAOYSA-N 6-[4-[(3,5-dimethoxyphenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n-ethyl-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CC=3C=C(OC)C=C(OC)C=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 KQEOSIGOXSGWBG-UHFFFAOYSA-N 0.000 description 1
BYQVNPYZOFTMQE-UHFFFAOYSA-N 6-[4-[(4-chlorophenyl)methyl]-5-methyl-3-oxo-1h-pyrazol-2-yl]-n,n-diethylpyridine-3-sulfonamide Chemical compound N1=CC(S(=O)(=O)N(CC)CC)=CC=C1N1C(=O)C(CC=2C=CC(Cl)=CC=2)=C(C)N1 BYQVNPYZOFTMQE-UHFFFAOYSA-N 0.000 description 1
FMEBIWNKYZUWFV-UHFFFAOYSA-N 6-chloropyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)N=C1 FMEBIWNKYZUWFV-UHFFFAOYSA-N 0.000 description 1
HBBSDZXXUIHKJE-UHFFFAOYSA-N 6-hydrazinylpyridine-3-carboxylic acid Chemical compound NNC1=CC=C(C(O)=O)C=N1 HBBSDZXXUIHKJE-UHFFFAOYSA-N 0.000 description 1
LODFJZCIJKBHNZ-UHFFFAOYSA-N 6-hydrazinylpyridine-3-sulfonamide Chemical compound NNC1=CC=C(S(N)(=O)=O)C=N1 LODFJZCIJKBHNZ-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
KXOGTQMEUZDLDZ-UHFFFAOYSA-N C1(=CC=CC=C1)C1=NC=CC=C1S(=O)(=O)N.Cl Chemical compound C1(=CC=CC=C1)C1=NC=CC=C1S(=O)(=O)N.Cl KXOGTQMEUZDLDZ-UHFFFAOYSA-N 0.000 description 1
102100034798 CCAAT/enhancer-binding protein beta Human genes 0.000 description 1
IHFHTEQUTSSHTH-UHFFFAOYSA-N CCCC(=O)C(C(O)=O)CC1=CC=CC=C1 Chemical compound CCCC(=O)C(C(O)=O)CC1=CC=CC=C1 IHFHTEQUTSSHTH-UHFFFAOYSA-N 0.000 description 1
206010006895 Cachexia Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
DLYXGWZARQTXHQ-UHFFFAOYSA-N Cl.CC=1NN(C(C1CC=1C=NC=CC1)=O)C1=CC=CCN1C(C)C Chemical compound Cl.CC=1NN(C(C1CC=1C=NC=CC1)=O)C1=CC=CCN1C(C)C DLYXGWZARQTXHQ-UHFFFAOYSA-N 0.000 description 1
WXXQFGBNYPLBMC-UHFFFAOYSA-N Cl.CC=1NN(C(C1CC=1C=NC=CC1)=O)C1=CC=CCN1C1=NC=CC=C1 Chemical compound Cl.CC=1NN(C(C1CC=1C=NC=CC1)=O)C1=CC=CCN1C1=NC=CC=C1 WXXQFGBNYPLBMC-UHFFFAOYSA-N 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
241001459693 Dipterocarpus zeylanicus Species 0.000 description 1
238000012286 ELISA Assay Methods 0.000 description 1
102000006402 Endocrine-Gland-Derived Vascular Endothelial Growth Factor Human genes 0.000 description 1
108010044063 Endocrine-Gland-Derived Vascular Endothelial Growth Factor Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
101000945963 Homo sapiens CCAAT/enhancer-binding protein beta Proteins 0.000 description 1
101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
108090000144 Human Proteins Proteins 0.000 description 1
102000003839 Human Proteins Human genes 0.000 description 1
GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
GLTQCXRDBXJHFK-UHFFFAOYSA-N N1=CC(S(=O)(=O)NC(C)(C)C)=CC=C1N1C(=O)C(C(CC(O)=O)C=2C=CC=CC=2)=CN1 Chemical compound N1=CC(S(=O)(=O)NC(C)(C)C)=CC=C1N1C(=O)C(C(CC(O)=O)C=2C=CC=CC=2)=CN1 GLTQCXRDBXJHFK-UHFFFAOYSA-N 0.000 description 1
229910017849 NH2—NH2 Inorganic materials 0.000 description 1
101100114416 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) con-10 gene Proteins 0.000 description 1
FRCUWAGWYJXREA-UHFFFAOYSA-N O=S(=C1C=NC(Cl)=CC1)=O.Cl Chemical compound O=S(=C1C=NC(Cl)=CC1)=O.Cl FRCUWAGWYJXREA-UHFFFAOYSA-N 0.000 description 1
241000950458 Oxandra laurifolia Species 0.000 description 1
206010033733 Papule Diseases 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
108700008625 Reporter Genes Proteins 0.000 description 1
241001275117 Seres Species 0.000 description 1
241000718541 Tetragastris balsamifera Species 0.000 description 1
229910003074 TiCl4 Inorganic materials 0.000 description 1
241000292525 Titanio Species 0.000 description 1
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
RNVYQYLELCKWAN-RXMQYKEDSA-N [(4r)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@@H](CO)O1 RNVYQYLELCKWAN-RXMQYKEDSA-N 0.000 description 1
RNVYQYLELCKWAN-YFKPBYRVSA-N [(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)OC[C@H](CO)O1 RNVYQYLELCKWAN-YFKPBYRVSA-N 0.000 description 1
VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 1
ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
238000010306 acid treatment Methods 0.000 description 1
YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
230000008649 adaptation response Effects 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000004183 alkoxy alkyl group Chemical group 0.000 description 1
125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 1
QYCSNMDOZNUZIT-UHFFFAOYSA-N benzhydrylidenehydrazine Chemical compound C=1C=CC=CC=1C(=NN)C1=CC=CC=C1 QYCSNMDOZNUZIT-UHFFFAOYSA-N 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
NWJBOTGGBYFKEJ-UHFFFAOYSA-M bromorhenium;carbon monoxide Chemical compound [O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[Re]Br NWJBOTGGBYFKEJ-UHFFFAOYSA-M 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
229940027138 cambia Drugs 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
239000006143 cell culture medium Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
229940092727 claro Drugs 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
238000004590 computer program Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
230000005595 deprotonation Effects 0.000 description 1
238000010537 deprotonation reaction Methods 0.000 description 1
KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 description 1
VUWPIBNKJSEYIN-UHFFFAOYSA-N diethyl 2-benzylidenepropanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CC1=CC=CC=C1 VUWPIBNKJSEYIN-UHFFFAOYSA-N 0.000 description 1
ZSANYRMTSBBUCA-UHFFFAOYSA-N diethyl 3-oxopentanedioate Chemical compound CCOC(=O)CC(=O)CC(=O)OCC ZSANYRMTSBBUCA-UHFFFAOYSA-N 0.000 description 1
WDJUZGPOPHTGOT-XUDUSOBPSA-N digitoxin Chemical class C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)CC5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O WDJUZGPOPHTGOT-XUDUSOBPSA-N 0.000 description 1
NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
VNEBWJSWMVTSHK-UHFFFAOYSA-L disodium;3-hydroxynaphthalene-2,7-disulfonate Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=CC2=C1 VNEBWJSWMVTSHK-UHFFFAOYSA-L 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
239000012039 electrophile Substances 0.000 description 1
210000001671 embryonic stem cell Anatomy 0.000 description 1
238000003173 enzyme complementation Methods 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
KQWWVLVLVYYYDT-UHFFFAOYSA-N ethyl 3-oxohexanoate Chemical compound CCCC(=O)CC(=O)OCC KQWWVLVLVYYYDT-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
230000022244 formylation Effects 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
238000002825 functional assay Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
230000002650 habitual effect Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
230000002489 hematologic effect Effects 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
229940097277 hygromycin b Drugs 0.000 description 1
239000007943 implant Substances 0.000 description 1
239000000411 inducer Substances 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000005291 magnetic effect Effects 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
WRAKFCLGWVROJC-ONEGZZNKSA-N methyl (e)-3-(5-methoxypyridin-3-yl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CN=CC(OC)=C1 WRAKFCLGWVROJC-ONEGZZNKSA-N 0.000 description 1
CFDQCVPDCRLEEO-UHFFFAOYSA-N methyl 2-[(2-chloro-6-fluorophenyl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=C(F)C=CC=C1Cl CFDQCVPDCRLEEO-UHFFFAOYSA-N 0.000 description 1
DMUOGYCUUQVHDC-UHFFFAOYSA-N methyl 2-[(3-hydroxyphenyl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CC=CC(O)=C1 DMUOGYCUUQVHDC-UHFFFAOYSA-N 0.000 description 1
OYGHYUKXWPZWMZ-UHFFFAOYSA-N methyl 2-[(5-cyanopyridin-3-yl)methyl]-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)CC1=CN=CC(C#N)=C1 OYGHYUKXWPZWMZ-UHFFFAOYSA-N 0.000 description 1
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
CTSAXXHOGZNKJR-UHFFFAOYSA-N methyl 2-diethoxyphosphorylacetate Chemical compound CCOP(=O)(OCC)CC(=O)OC CTSAXXHOGZNKJR-UHFFFAOYSA-N 0.000 description 1
YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
XACCBAOLPSUDEG-UHFFFAOYSA-N methyl 3-oxo-2-(2-phenylethyl)butanoate Chemical compound COC(=O)C(C(C)=O)CCC1=CC=CC=C1 XACCBAOLPSUDEG-UHFFFAOYSA-N 0.000 description 1
FQRRQPZYIYAPAV-UHFFFAOYSA-N methyl 3-pyridin-3-ylpropanoate Chemical compound COC(=O)CCC1=CC=CN=C1 FQRRQPZYIYAPAV-UHFFFAOYSA-N 0.000 description 1
IIHIJFJSXPDTNO-UHFFFAOYSA-N methyl cyclopentanecarboxylate Chemical compound COC(=O)C1CCCC1 IIHIJFJSXPDTNO-UHFFFAOYSA-N 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
239000002395 mineralocorticoid Substances 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
QOOZNVBEEKFWHK-UHFFFAOYSA-N n-(2,2,2-trifluoroethyl)propanamide Chemical compound CCC(=O)NCC(F)(F)F QOOZNVBEEKFWHK-UHFFFAOYSA-N 0.000 description 1
WBUCQUQYYQPBFL-UHFFFAOYSA-N n-ethyl-6-[4-[(5-methoxypyridin-3-yl)methyl]-3-oxo-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide;hydrochloride Chemical compound Cl.C=1C=C(N2C(C(CC=3C=C(OC)C=NC=3)=CN2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 WBUCQUQYYQPBFL-UHFFFAOYSA-N 0.000 description 1
ZIIUPNNDVSYRHP-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(3-phenylpropyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide Chemical compound C=1C=C(N2C(C(CCCC=3C=CC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 ZIIUPNNDVSYRHP-UHFFFAOYSA-N 0.000 description 1
DJTVQQLMPUKPEF-UHFFFAOYSA-N n-ethyl-6-[5-methyl-3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]-n-phenylpyridine-3-sulfonamide;hydrochloride Chemical compound Cl.C=1C=C(N2C(C(CC=3C=NC=CC=3)=C(C)N2)=O)N=CC=1S(=O)(=O)N(CC)C1=CC=CC=C1 DJTVQQLMPUKPEF-UHFFFAOYSA-N 0.000 description 1
XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
JQEKDNLKIVGXAU-UHFFFAOYSA-L nedocromil sodium Chemical compound [Na+].[Na+].CCN1C(C([O-])=O)=CC(=O)C2=C1C(CCC)=C1OC(C([O-])=O)=CC(=O)C1=C2 JQEKDNLKIVGXAU-UHFFFAOYSA-L 0.000 description 1
KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
239000012285 osmium tetroxide Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
229940037129 plain mineralocorticoids for systemic use Drugs 0.000 description 1
230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
230000002265 prevention Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000004224 protection Effects 0.000 description 1
230000001012 protector Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
238000012216 screening Methods 0.000 description 1
150000003355 serines Chemical class 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
QTENRWWVYAAPBI-YCRXJPFRSA-N streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O QTENRWWVYAAPBI-YCRXJPFRSA-N 0.000 description 1
238000013456 study Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
JGYKFRBCNFOTMQ-UHFFFAOYSA-N tert-butyl 6-[5-methyl-3-oxo-4-(pyridin-3-ylmethyl)-1h-pyrazol-2-yl]pyridine-3-carboxylate Chemical compound O=C1C(CC=2C=NC=CC=2)=C(C)NN1C1=CC=C(C(=O)OC(C)(C)C)C=N1 JGYKFRBCNFOTMQ-UHFFFAOYSA-N 0.000 description 1
ATFRHOQYDNQILY-JKSUJKDBSA-N tert-butyl n-[(1r,3s)-3-(phenylmethoxymethyl)cyclopentyl]carbamate Chemical compound C1[C@H](NC(=O)OC(C)(C)C)CC[C@@H]1COCC1=CC=CC=C1 ATFRHOQYDNQILY-JKSUJKDBSA-N 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
102100035070 von Hippel-Lindau disease tumor suppressor Human genes 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6875—Nucleoproteins
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Biomedical Technology (AREA)
Immunology (AREA)
Cardiology (AREA)
Molecular Biology (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
General Physics & Mathematics (AREA)
Biochemistry (AREA)
Pathology (AREA)
Analytical Chemistry (AREA)
Physics & Mathematics (AREA)
Food Science & Technology (AREA)
Microbiology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biotechnology (AREA)
Cell Biology (AREA)
Ophthalmology & Optometry (AREA)
Obesity (AREA)
Hospice & Palliative Care (AREA)
Emergency Medicine (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Endocrinology (AREA)

ES09805789.6T 2008-12-29 2009-12-24 Derivados de 2-piridin-2-il-pirazol-3(2H)-ona, su preparación y uso terapéutico como activadores de HIF Active ES2481042T3 (es)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
FR0807474		2008-12-29
FR0807474A FR2940651B1 (fr)	2008-12-29	2008-12-29	Derives de 2-pyridin-2-yl-pyrazol-3(2h)-one,leur preparation et leur application en therapeutique comme activateurs de hif
FR0904092A FR2949466A1 (fr)	2009-08-28	2009-08-28	Derives de 2-pyridin-2-yl-pyrazol-3(2h)-one, leur preparation et leur application en therapeutique comme activateurs de hif
FR0904092		2009-08-28
PCT/FR2009/052691 WO2010076524A2 (fr)	2008-12-29	2009-12-24	Derives de 2-pyridin-2-yl-pyrazol-3(2h)-one, leur preparation et leur application en therapeutique comme activateurs de hif

Publications (1)

Publication Number	Publication Date
ES2481042T3 true ES2481042T3 (es)	2014-07-29

Family

ID=42008610

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES09805789.6T Active ES2481042T3 (es)	2008-12-29	2009-12-24	Derivados de 2-piridin-2-il-pirazol-3(2H)-ona, su preparación y uso terapéutico como activadores de HIF

Country Status (35)

Country	Link
US (1)	US8541455B2 (fr)
EP (1)	EP2382205B1 (fr)
JP (1)	JP5734870B2 (fr)
KR (1)	KR20110099786A (fr)
CN (1)	CN102333769B (fr)
AR (1)	AR074915A1 (fr)
AU (1)	AU2009334569B2 (fr)
BR (1)	BRPI0924060A8 (fr)
CA (1)	CA2748411A1 (fr)
CL (1)	CL2011001496A1 (fr)
CO (1)	CO6400141A2 (fr)
CR (1)	CR20110361A (fr)
CY (1)	CY1115368T1 (fr)
DK (1)	DK2382205T3 (fr)
EA (1)	EA019591B1 (fr)
EC (1)	ECSP11011155A (fr)
ES (1)	ES2481042T3 (fr)
HR (1)	HRP20140680T1 (fr)
IL (1)	IL213789A (fr)
MA (1)	MA32976B1 (fr)
MX (1)	MX2011007054A (fr)
MY (1)	MY179093A (fr)
NZ (1)	NZ593751A (fr)
PA (1)	PA8856201A1 (fr)
PE (1)	PE20120416A1 (fr)
PL (1)	PL2382205T3 (fr)
PT (1)	PT2382205E (fr)
SG (1)	SG172803A1 (fr)
SI (1)	SI2382205T1 (fr)
SM (1)	SMT201400097B (fr)
TN (1)	TN2011000267A1 (fr)
TW (1)	TWI482763B (fr)
UY (1)	UY32369A (fr)
WO (1)	WO2010076524A2 (fr)
ZA (1)	ZA201104783B (fr)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN102333776B (zh)	2008-12-29	2014-05-21	赛诺菲	2-吡啶-2-基-吡唑-3(2h)-酮的衍生物、其制备和治疗用途
JP5902671B2 (ja) *	2011-03-31	2016-04-13	キッセイ薬品工業株式会社	ベンジルピラゾール誘導体の製造方法およびその製造中間体
ES2699404T3 (es)	2012-03-30	2019-02-11	Daiichi Sankyo Co Ltd	Derivado de 4-alcanoilamino-3-pirazolona
EP3336084B1 (fr) *	2013-03-29	2021-03-17	Takeda Pharmaceutical Company Limited	Dérivés de 6-(5-hydroxy-1h-pyrazol-1-yl) nicotinamide et leur utilisation en tant qu'inhibiteurs de phd
DE102016223133A1 (de)	2016-11-23	2018-05-24	Deere & Company	Geschwindigkeitskontrolle einer Erntemaschine
CN121085893A (zh) *	2020-03-20	2025-12-09	阿克比治疗有限公司	Phd抑制剂化合物、组合物和用途

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4023488A1 (de) *	1990-07-24	1992-01-30	Bayer Ag	1-(pyri(mi)dyl-(2)) -5-hydroxy-pyrazol-mikrobizide
US5750088A (en)	1993-03-30	1998-05-12	The Dupont Merck Pharmaceutical Company	Stable hydrazones linked to a peptide moiety as reagents for the preparation of radiopharmaceuticals
JP4499721B2 (ja)	2003-06-30	2010-07-07	ヒフバイオ，インク．	化合物、組成物および方法
DE102005019712A1 (de)	2005-04-28	2006-11-09	Bayer Healthcare Ag	Dipyridyl-dihydropyrazolone und ihre Verwendung
PE20071020A1 (es)	2006-03-07	2007-12-11	Smithkline Beecham Corp	Compuestos derivados de glicina n-sustituidos como inhibidores de prolil hidroxilasa
KR20090066297A (ko)	2006-10-16	2009-06-23	화이자 프로덕츠 인크.	치료용 피라졸릴 티에노피리딘
DE102006050516A1 (de) *	2006-10-26	2008-04-30	Bayer Healthcare Ag	Substituierte Dihydropyrazolone und ihre Verwendung
US8796253B2 (en)	2007-05-18	2014-08-05	Bayer Intellectual Property Gmbh	Heteroaryl substituted pyrazole derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis

2009
- 2009-12-24 KR KR1020117017676A patent/KR20110099786A/ko not_active Abandoned
- 2009-12-24 PL PL09805789T patent/PL2382205T3/pl unknown
- 2009-12-24 DK DK09805789.6T patent/DK2382205T3/da active
- 2009-12-24 MY MYPI2011003012A patent/MY179093A/en unknown
- 2009-12-24 HR HRP20140680AT patent/HRP20140680T1/hr unknown
- 2009-12-24 BR BRPI0924060A patent/BRPI0924060A8/pt not_active IP Right Cessation
- 2009-12-24 MX MX2011007054A patent/MX2011007054A/es active IP Right Grant
- 2009-12-24 AU AU2009334569A patent/AU2009334569B2/en not_active Ceased
- 2009-12-24 JP JP2011542886A patent/JP5734870B2/ja not_active Expired - Fee Related
- 2009-12-24 NZ NZ593751A patent/NZ593751A/xx not_active IP Right Cessation
- 2009-12-24 MA MA34027A patent/MA32976B1/fr unknown
- 2009-12-24 SG SG2011047503A patent/SG172803A1/en unknown
- 2009-12-24 ES ES09805789.6T patent/ES2481042T3/es active Active
- 2009-12-24 PT PT98057896T patent/PT2382205E/pt unknown
- 2009-12-24 SI SI200930983T patent/SI2382205T1/sl unknown
- 2009-12-24 EP EP09805789.6A patent/EP2382205B1/fr active Active
- 2009-12-24 CN CN200980157590.6A patent/CN102333769B/zh not_active Expired - Fee Related
- 2009-12-24 EA EA201170899A patent/EA019591B1/ru not_active IP Right Cessation
- 2009-12-24 CA CA2748411A patent/CA2748411A1/fr not_active Abandoned
- 2009-12-24 PE PE2011001292A patent/PE20120416A1/es not_active Application Discontinuation
- 2009-12-24 WO PCT/FR2009/052691 patent/WO2010076524A2/fr not_active Ceased
- 2009-12-28 AR ARP090105126A patent/AR074915A1/es unknown
- 2009-12-28 TW TW098145336A patent/TWI482763B/zh not_active IP Right Cessation
- 2009-12-29 PA PA20098856201A patent/PA8856201A1/es unknown
- 2009-12-29 UY UY0001032369A patent/UY32369A/es not_active Application Discontinuation
2011
- 2011-05-24 TN TN2011000267A patent/TN2011000267A1/fr unknown
- 2011-06-17 CL CL2011001496A patent/CL2011001496A1/es unknown
- 2011-06-22 EC EC2011011155A patent/ECSP11011155A/es unknown
- 2011-06-23 CR CR20110361A patent/CR20110361A/es unknown
- 2011-06-27 IL IL213789A patent/IL213789A/en not_active IP Right Cessation
- 2011-06-28 ZA ZA2011/04783A patent/ZA201104783B/en unknown
- 2011-06-29 US US13/172,305 patent/US8541455B2/en not_active Expired - Fee Related
- 2011-06-29 CO CO11081326A patent/CO6400141A2/es active IP Right Grant
2014
- 2014-07-22 SM SM201400097T patent/SMT201400097B/xx unknown
- 2014-07-23 CY CY20141100553T patent/CY1115368T1/el unknown

Also Published As

Publication number	Publication date
PA8856201A1 (es)	2010-07-27
CN102333769A (zh)	2012-01-25
ECSP11011155A (es)	2011-07-29
AU2009334569B2 (en)	2016-02-25
BRPI0924060A8 (pt)	2015-09-29
IL213789A0 (en)	2011-07-31
KR20110099786A (ko)	2011-09-08
AR074915A1 (es)	2011-02-23
CY1115368T1 (el)	2017-01-04
CN102333769B (zh)	2014-08-27
TWI482763B (zh)	2015-05-01
UY32369A (es)	2010-07-30
ZA201104783B (en)	2012-09-26
WO2010076524A2 (fr)	2010-07-08
MA32976B1 (fr)	2012-01-02
CL2011001496A1 (es)	2011-10-28
CR20110361A (es)	2011-09-20
PE20120416A1 (es)	2012-05-08
DK2382205T3 (da)	2014-07-28
BRPI0924060A2 (pt)	2015-07-07
IL213789A (en)	2014-11-30
SMT201400097B (it)	2014-09-08
SG172803A1 (en)	2011-08-29
EP2382205A2 (fr)	2011-11-02
JP2012513976A (ja)	2012-06-21
TN2011000267A1 (fr)	2012-12-17
MY179093A (en)	2020-10-27
HRP20140680T1 (hr)	2014-10-10
EA019591B1 (ru)	2014-04-30
AU2009334569A1 (en)	2011-07-21
EP2382205B1 (fr)	2014-04-23
PT2382205E (pt)	2014-07-28
NZ593751A (en)	2013-08-30
PL2382205T3 (pl)	2014-09-30
CO6400141A2 (es)	2012-03-15
CA2748411A1 (fr)	2010-07-08
US20110294788A1 (en)	2011-12-01
US8541455B2 (en)	2013-09-24
WO2010076524A3 (fr)	2010-08-26
JP5734870B2 (ja)	2015-06-17
TW201028391A (en)	2010-08-01
SI2382205T1 (sl)	2014-08-29
EA201170899A1 (ru)	2012-02-28
MX2011007054A (es)	2011-11-29

Publication	Publication Date	Title
ME01296B (me)	2013-12-20	Derivati 4-(2-amino-1-hidroksietil) fenol kao agonisti beta-2 adrenergičkih receptora
ES2672530T3 (es)	2018-06-14	Amidas heterocíclicas como inhibidores de cinasas
ES2481042T3 (es)	2014-07-29	Derivados de 2-piridin-2-il-pirazol-3(2H)-ona, su preparación y uso terapéutico como activadores de HIF
ES2259419T3 (es)	2006-10-01	Imidazo(1,2-a)piridinas.
US9359329B2 (en)	2016-06-07	Derivatives of 2-pyridin-2-yl-pyrazol-3(2H)-one, preparation and therapeutic use thereof
ME00979B (me)	2012-06-20	DERIVATI INDOL-2-ONA, DISUPSTITUISANI NA 3-POZICIJI, NJIHOVO DOBIJANJE l PRIMJENA U TERAPIJI
ES2976567T3 (es)	2024-08-05	Formas cristalinas de (1-pirimidin-2-il-ciclopropil)-amida del ácido (3S,4S)-1-ciclopropilmetil-4-{[5-(2,4-difluoro-fenil)-isoxazol-3-carbonil]-amino}-piperidin-3-carboxílico
JP2024540428A (ja)	2024-10-31	分解剤及びその使用
HK1163678A (en)	2012-09-14	Derivatives of 2-pyridin-2-yl-pyrazol-3(2h)-one, preparation and therapeutic use thereof as hif activators
HK1163678B (en)	2014-11-21	Derivatives of 2-pyridin-2-yl-pyrazol-3(2h)-one, preparation and therapeutic use thereof as hif activators
HK1163679B (en)	2015-05-08	Derivatives of 2-pyridin-2-yl-pyrazol-3(2h)-one, preparation and therapeutic use thereof
FR2949466A1 (fr)	2011-03-04	Derives de 2-pyridin-2-yl-pyrazol-3(2h)-one, leur preparation et leur application en therapeutique comme activateurs de hif